Practical Dialysis in the Year 2009

Practical Dialysis in the Year 2009 4.3.4 °“√ ÕπºªŸâ É«¬ (Patient Teaching) 1. ºŸâªÉ«¬§«√‰¥â√—∫°“√ Õπ„Àâ∫√‘À“√√¬“ߧå∑’Ë¡’ AVG ‚¥¬°“ß·¢π·≈–Àÿ∫·¢π·≈–„™â·¢π μ“¡ª°μ‘‡∑à“∑’Ë®–∑”‰¥â‡æ◊Ëՙ૬°“√‰À≈‡«’¬π°≈—∫¢Õ߇≈◊Õ¥¥” ·≈–≈¥°“√∫«¡ 2. À≈’°‡≈’ˬ߰“√‡®“–‡≈◊Õ¥·≈–«—¥§«“¡¥—π‚≈À‘μ·¢π∑’Ë¡’ AV graft 3. °“√§≈” thrill ¢Õß AV graft 4. À≈’°‡≈’ˬ߰“√πÕπÀπÿπ·¢π∑’Ë¡’ AV graft À√◊ÕπÕπ∑—∫ 5. À≈’°‡≈’ˬ߰“√ «¡„ à ‘Ëß°¥√—¥μàÕ AV graft ‡™àπ °”‰√ ‡§√◊ËÕߪ√–¥—∫ π“Ãî°“ ºà“æ—π·º≈ ‡ªìπμâπ 6. „Àâ∑”§«“¡ –Õ“¥·¢π¥â«¬ ∫àŸ¬“¶à“‡™◊ÈÕ°àÕπ°“√·∑߇¢Á¡ 7. ·πà„®«à“∫ÿ§≈“°√‰μ‡∑’¬¡∑”°“√¶à“‡™◊ÈÕÕ¬à“ß ¡∫√Ÿ ≥å°àÕπ°“√·∑߇¢Á¡ 8. ¬È”„Àâ∫ÿ§≈“°√‰μ‡∑’¬¡‡ª≈’ˬπ∑’Ë·∑߇¢Á¡ 9. °¥À“â ¡‡≈Õ◊ ¥¥«â ¬·√ß¥π— ‡©æ“–∑∑Ë’ ‡Ë’ À¡“– ¡ ‚¥¬¬ß— ¡Õ’ μ— √“‰À≈¢Õ߇≈Õ◊ ¥„π‡ πâ graft Õ¬Ÿà μ≈Õ¥‡«≈“ 10. √“¬ß“πÀÕâ ߉μ‡∑¬’ ¡À√Õ◊ ÀÕâ ß©°ÿ ‡©π‘ ‡æÕ◊Ë ¢Õ§«“¡™«à ¬‡À≈Õ◊ ‡¡Õ◊Ë ¡‡’ ≈Õ◊ ¥ÕÕ°·≈–ºªâŸ «É ¬μÕâ ß  “¡“√∂Àâ“¡‡≈◊Õ¥¥â«¬μπ‡Õ߉¥â∂Ÿ°μâÕß 11. °“√√“¬ß“πÕ“°“√·≈–Õ“°“√· ¥ß¢Õß°“√μ‘¥‡™◊ÈÕ ‰¡àæ∫ thrill ‰¡à‰¥â¬‘π‡ ’¬ß bruit 12. «—¥Õÿ≥À¿¡Ÿ ‘¢Õß√à“ß°“¬ ¡Ë”‡ ¡Õ·≈–√“¬ß“π∑—π∑’∑’Ë¡’‰¢â 13. √“¬ß“π‡¡◊ËÕæ∫«à“¡’¢Õ߇À≈«´÷¡À√◊Õ¡’‡≈◊Õ¥ÕÕ°º‘¥ª°μ‘®“° graft „π∑—π∑’ 14. ·®ßâ „Àæâ ¬“∫“≈∑√“∫∂ß÷ °“√π¥— ∑”Àμ— ∂°“√∑¡’Ë ’invasive ‡æÕ◊Ë √“¬ß“π·æ∑¬„å À¬â “ªØ™‘ «’ π– ªÑÕß°—π°“√μ‘¥‡™◊ÈÕ°àÕπ°“√∑” 5. °“√‡Ω“Ñ √–«—ß Vascular access (Vascular access surveillance) 20,21 °“√‡Ω“Ñ √–«ß— ª√–°Õ∫¥«â ¬°“√ª√–‡¡π‘ ‡ πâ ‡≈Õ◊ ¥°“√«π‘ ®‘ ©¬— ¿“«–·∑√°´Õâ π·≈–°“√·°ªâ ≠í À“ ‚¥¬¡’‡ªÑ“À¡“¬‡æ◊ËÕ‡æ‘Ë¡Õ“¬ÿ°“√„™âß“π¢Õß vascular access ∑ÿ°ª√–‡¿∑ „Àâ¡’°“√«‘π‘®©—¬Õ“°“√μ’∫°àÕπ μ—π‰¥â¡“°¬‘Ëߢ÷Èπ ‡æ‘Ë¡®”π«π°“√ àßμàպ⟪ɫ¬‡æ◊ËÕ∑” angioplasty À√◊Õºà“μ—¥´àÕ¡·´¡·μà‡π‘ËπÊ ·≈–≈¥°“√ „™â CVC 5.1 °“√ª√–‡¡‘π∑“ߧ≈π‘ ‘° (Clinical assessment) 5.1.1 ∑ÿ° —ª¥“Àå·≈–∫—π∑÷°√“¬ß“π 5.1.2 °“√ —߇°μ (observation) - Õ“°“√∫«¡‰¡à¬ÿ∫ (persistent swelling) - ‡≈◊Õ¥À¬ÿ¥¬“°À≈—ß HD - Thrombosis À√◊Õ clots ∑’Ëæ∫„π vascular access ¢≥–·∑߇¢Á¡ - Õ“°“√·≈–Õ“°“√· ¥ß¢Õß°“√μ‘¥‡™◊ÈÕ 138

Pitfalls in Vascular Access for Dialysis Nurses - °“√‡ª≈’ˬπ·ª≈ߢÕß vascular access À√◊Õ √¬“ߧå∑’Ë¡’ vascular access - Prepump arterial pressure ∑’ˠߟ ¢÷Èπ 5.1.3 °“√§≈” / øíß (Palpation / Auscultation) - Bruit / Thrill ∑’Ëμ”·Àπàß arterial, middle, venous ¢Õß vascular access (1) §≈” thrill ‰¥âÀ¡¥∑—Èß 3 μ”·Àπàß · ¥ß«à“ blood flow > 450 ml/min (2) §≈”‰¥â‡©æ“– pulse · ¥ß«à“¡’ blood flow < 450 ml/min (3) ‡ ’¬ß bruit ∑’Ë¥—ß¡“° · ¥ß«à“ ¡’ stricture À√◊Õ stenosis - ¡’°“√‡ª≈’ˬπ≈—°…≥–‰ª¢Õß bruit / thrill - ª√–‡¡π‘ Õ≥ÿ À¿¡Ÿ ‘ Õ“°“√ª«¥ §«“¡√ âŸ °÷ ∑≈’Ë ¥≈ß (™“) ∑ª’Ë ≈“¬√¬“ߧ∑å ¡’Ë ’ vascular access ∑ÿ° 1 ‡¥◊Õπ 5.2 Monitoring methods 5.2.1 Dynamic Venous Pressure - ¡’§«“¡‡∑’ˬßμ√ß §à“„™â®à“¬πâÕ¬ - æ√âÕ¡∑’Ë®”∑”‰¥â∑—π∑’ - «‘π‘®©—¬Õ“°“√μ’∫¢Õß native fistula ∑’ˇ°‘¥®“° collateral vein ‰¥â‰¡à¥’ - μâÕß„™â§à“ 3 §à“ ¢÷Èπ‰ª °”Àπ¥ threshold - ∑”∑ÿ° 1  —ª¥“Àå 5.2.2 Static Venous Pressure - ¡’§«“¡‡∑’ˬßμ√ß §à“„™â®à“¬πâÕ¬ - æ√âÕ¡∑’Ë®–∑”‰¥â∑—π∑’ - «‘π‘®©—¬Õ“°“√μ’∫¢Õß native fistula ∑’ˇ°‘¥®“° collateral vein ‰¥â‰¡à¥’ - ∑”∑ÿ° 2  —ª¥“Àå 5.2.3 Recirculation studies - «π‘ ®‘ ©¬— Õ“°“√μ∫’ ¢Õß native fistula ‰¥¥â °’ «“à ‡πÕ◊Ë ß®“° native fistula¬ß— §ßª√– ∑‘ ∏¿‘ “æ ‰¥â∑’Ë blood flow μË”°«à“ graft - late predictor of stenosis (1) recirculation > 10% §«√ àß∑” angiogram (2) recirculation > 20% §«√μ√«®°“√·∑߇¢Á¡∑—π∑’ 5.3 Data tracking 5.3.1 Monitoring test - URR - Kt/V - angiogram 139

Practical Dialysis in the Year 2009 - Doppler ultrasound 5.3.2 Clinical assessment 5.3.3 Incidence of thrombosis 5.3.4 Incidence of infection 5.4 Intervention tracking 5.4.1 Angioplasty - > 50% unassited patency at 6 months - < 30% residual stenosis after procedure 5.4.2 Surgical revision: > 50% unassited patency at 1 yr 5.5 Quality improvement 5.5.1 Thrombosis 5.5.2 Stenosis 5.5.3 Infection 5.5.4 Response of staff and patients to education 6. Clinical outcome goals22 KDOQI Clinical Practice Guidelines and Recommendations for Vascular Access 2006 6.1 AV Fistula - Maximizing AV fistula placement, at least 65% of all patients new to hemodialysis - Prevalent function AV fistula placement rate > 65% of patients - The long-term rate of AV fistula thrombosis < 0.25 episodes/patient year at risk - The rate of AV fistula infection < 1% during the use-life of the access 6.2 AV Graft - The rate of AV graft thrombosis < 0.5 episodes/patient year at risk - The cumulative patency rate of all AV graft, at least One year 70% Two years 60% Three years 50% - The rate of AV graft infection < 10 % during the use-life of the access. 140

Pitfalls in Vascular Access for Dialysis Nurses 6.3 Central Venous Catheter - Cuffed catheter for permanent dialysis access < 10% of patients - Tunneled catheter-related infection < 10% at 3 months, < 50% at 1 year 7.  √ªÿ Vascular access ‡ªìπ™àÕß∑“ß„π°“√π”‡≈◊Õ¥®“°μ—«ºâŸªÉ«¬‚√§‰μ‡√◊ÈÕ√—ß ‡¢â“ Ÿà«ß®√‰μ‡∑’¬¡„π ¢∫«π°“√øÕ°‡≈Õ◊ ¥¥«â ¬‡§√Õ◊Ë ß‰μ‡∑¬’ ¡ ‡æÕ◊Ë °“√∫”∫¥— ∑¥·∑π‰μ„Àºâ ªŸâ «É ¬¡™’ «’ μ‘ ¬π◊ ¬“«μÕà ‰ª ∂“â ª√“»®“° vascular access ¢∫«π°“√π’È°Á‡°‘¥¢÷Èπ‰¡à‰¥â 欓∫“≈‰μ‡∑’¬¡‡ªìπºŸâ¡’∫∑∫“∑„π°“√„™â·≈–¥·Ÿ ≈ vascular access ‚¥¬μ√ß ®÷ßμâÕß¡’§«“¡√Ÿâ§«“¡‡¢â“„®„π vascular access ∑ÿ°™π‘¥  “¡“√∂ª√–‡¡‘π°“√∑”ß“π∑’Ë ª°μ‘ ª√–‡¡‘π¿“«–·∑√°´âÕπ¢Õß∑’ˇ°‘¥¢÷Èπ·μàμâπ·≈–·°âªí≠À“‰¥âÕ¬à“߇À¡“– ¡  “¡“√∂«“ß·ºπ°“√ „™·â ≈–ªÕÑ ß°π— ª≠í À“∑®Ë’ –‡°¥‘ °∫— vascular access ‰¥¡â “°∑ Ë’ ¥ÿ °®Á –∑”„Àâ vascular access ¢ÕߺªâŸ «É ¬¡Õ’ “¬ÿ °“√„™âß“π‰¥â¬◊𬓫 ·≈–¡’ª√– ‘∑∏‘¿“楒 ≈¥¿“«–·∑√°´âÕπμà“ßÊ „ÀâÕ¬àŸ„π‡°≥±å¡“μ√∞“π‰¥â  àߺ≈ „À⇰‘¥°“√øÕ°‡≈◊Õ¥∑’ˇ撬ßæÕμàÕºŸâªÉ«¬ ∑”„À⺟âªÉ«¬·¢Áß·√ß ¡’§ÿ≥¿“æ™’«‘μ∑’Ë¥’Õ’°™àÕß∑“ßÀπ÷Ëß ·≈–¬—ß ‡ªìπ°“√™à«¬≈¥§à“„™â®à“¬¢Õߺ⟪ɫ¬·≈–¿“§√—∞„π°“√„™â√—°…“‰¥â‡ªìπÕ¬à“ß¡“° ‡Õ° “√Õ“â ßÕß‘ 1. Feldman HI, Kobrin S, Wasserstein A: Hemodialysis vascular access morbidity. J Am Soc Nephrol 1996; 7: 523-535. 2. Woods JD, Port FK. The impact of vascular access for hemodialysis on patient morbidity and mortality. Nephrol Dial Transplant. 1997; 12:657-659. 3. Dhingra RK, Young EW, Huibert-Shearon TE, Leavey SF, Port FK. Type of vascular access and mortality in U.S. hemodialysis patients. Kidney Int . 2001; 60:1443-1451. 4. Larry E.L. Core Curriculum for Nephrology Nursing. 4th ed. American Nephrology Nurses Association, New Jersey. 2001; 11: 307-3273. 5. Ayarragaray JE. Surgical treatment of hemodialysis-related central venous stenosis or occlusion: another option to maintain vascular access. J Vasc Surg. 2003;37:1043-6. 6. John TD, peter GB, Todd SI. Handbook of Dialysis. 4th ed. Lippincott Williams & Wilkins, Philadelphia. 2007; 6:87- 104. 7. Polkinghome KR, McDonald SP, Arkins RC, Kerr PG. Vascular access and all-cause morbidity: A propensity score analysis.J Am Soc Nephrol. 2004; 5:477-486. 8. Ryan SV, Calligaro KD, Dougherty MJ. Management of hemodialysis access infections. Semin Vasc Surg 2004;17(1):40- 4. 9. Schwab SJ, Quarles LD, Middleton JP, Cohan RH, Saeed M, Dennis VW. Hemodialysis-associated subclavian vein stenosis. Kidney Int 1988; 33:1156-1159 (evidence level: B). 10. NKF-K/DOQI Clinical Practice Guidelines for Vascular Access: update 2000. Am J Kidney Dis 2001; 37 (Suppl.1): S137-S181. 11. Levy J, Morgan J, Brown E. Vascular access: overview. In: Oxford handbook of Dialysis. New York, Oxford University Press. 2001; 102-123. 141

Practical Dialysis in the Year 2009 12. Kaufman JS, OûConnor TZ, Zhang JH, Cronin RE, Fiore LD, Ganz MB, Goldfarb DS, Peduzzi PN. Veterans Affairs Cooperative Study Group on Hemodialysis Access Graft Thrombosis. Randomized controlled trial of clopidogrel plus aspirin to prevent hemodialysisaccess graft thrombosis. J Am Soc Nephrol 2003;14:2313-21. 13. Wixon CL, Hughes JD, Mills JL. Understanding strategies for the treatment of ischemic steal syndrome after hemodialysis access. J Am Coll Surg. 2000;191:301-10. 14. Silva MB Jr, Hobson RW, Pappas PJ, Jamil Z, Araki CT, Goldberg MC, Gwertzman G, Padberg FT Jr. A strategy for increasing use of autogenous hemodialysis access procedures: impact of preoperative noninvasive evaluation. J Vasc Surg 1998; 27:302-307 (evidence level: B). 15. Albers FJ. Causes of hemodialysis access failure. Advances in renal replacement therapy,1994; 1:107-118. 16. Hawins CT. Nursesû role in influencing positive vascular access outcomes. ANNA journal.1995; 22(2), 127-129. 17. Safa AA, Valji K, Roberts AC, Zieger TW, Hye RJ, Oglevie SB. Detection and treatment of dysfunction hemodialysis access graft, 1996; 199(3): 653-657. 18. Turmel-Rodrigues L, Raynaud A, Bourquelot P. Percutaneous treatment of arteriovenous access dysfunction. In: Conlon PJ, Schwab SJ, Nicholson ML, eds. Hemodialysis Vascular Access: Practice and Problems. Oxford University Press, Oxford, New York: 2000: 183-202. 19. Twardowski ZJ. Constant Site (Buttonhole) Method of Needle Insertion for Hemodialysis. Dialysis & Transplantation 1995; 24:559-560-576. 20. Schwab SJ, Raymond JR, Saeed M, Newman GE, Dennis PA, Bollinger RR. Prevention of hemodialysis fistula thrombosis. Early detection of venous stenoses. Kidney Int 1989; 36:707-711. 21. McDougal G, Agarwal R. Clinical performance characteristics of hemodialysis graft monitoring. Kidney Int 2001; 60:762-766 (evidence level: B). 22. NKF-K/DOQI Clinical Practice Guidelines for Vascular Access: update 2006. Am J Kidney Dis 2006; 48 (Suppl.1): S258-S263. 142

Practical Guidelines to Reduce Cardiovascular Risk of Dialysis Patients 8 Practical Guidelines to Reduce Cardiovascular Risk of Dialysis Patients »ÿ¿ƒ°…å ®μ‘ μ°‘ “ππ∑å 1. ∫∑π” 2. ‚√§À—«„®·≈–À≈Õ¥‡≈Õ◊ ¥„πºªâŸ «É ¬‚√§‰μ‡√È◊Õ√—ß 3. °“√ªÕÑ ß°π— °“√‡°¥‘ ‚√§À«— „®·≈–À≈Õ¥‡≈Õ◊ ¥„πºâªŸ «É ¬øÕ°‡≈Õ◊ ¥ 4.  “‡Àμÿ∑’Ë°“√»÷°…“‡°’ˬ«°—∫‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥„πºâŸªÉ«¬ øÕ°‡≈Õ◊ ¥‰¡à‰¥âº≈ 5. Practical guidelines for prevention cardiovascular disease in dialysis patients 6.  √ÿª 143

Practical Dialysis in the Year 2009 1. ∫∑π” ‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥‡ªì𠓇Àμÿ°“√‡ ’¬™’«‘μ∑’Ë ”§—≠∑’Ë ÿ¥¢Õߺ⟪ɫ¬‚√§‰μ√–¬– ÿ¥∑⓬ ∑’ˉ¥â√—∫°“√√—°…“∑¥·∑π‰μ ‚¥¬æ∫«à“‡ªì𠓇Àμÿ¢Õß°“√‡ ’¬™’«‘μ Ÿß∂÷ß√âÕ¬≈– 40 ·≈– 42.2 ®“°¢âÕ¡Ÿ≈ ≈à“ ÿ¥„πªï §.». 2006 ¢Õߪ√–‡∑»ÕÕ ‡μ√‡≈’¬·≈–π‘«´’·≈π¥å ·≈–ª√–‡∑» À√—∞Õ‡¡√‘°“μ“¡≈”¥—∫1, 2 ªí®®ÿ∫—π‡ªìπ∑’Ë∑√“∫°—π¥’«à“‚√§‰μ‡√◊ÈÕ√—߇ªìπªí®®—¬‡ ’ˬß∑’Ë ”§—≠¢Õß‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥ ‚¥¬‡©æ“– ‡¡◊ËÕ‡¢â“ àŸ‚√§‰μ√–¬– ÿ¥∑⓬ ºâŸªÉ«¬®–¡’§«“¡‡ ’ˬßμàÕ°“√‡ ’¬™’«‘μ®“°‚√§À—«„® Ÿß¢÷Èπ 10-20 ‡∑à“‡¡◊ËÕ ‡∑¬’ ∫°∫— ª√–™“°√‡æ» ·≈–™«à ßÕ“¬‡ÿ ¥¬’ «°π— 3, 4 ®“°¢Õâ ¡≈Ÿ ¢Õß the Wave 2 Dialysis Morbidity and Mortality Study5 ´÷Ëß∑”°“√»÷°…“„πºŸâªÉ«¬∑’ˉ¥â√—∫°“√øÕ°‡≈◊Õ¥ 4,024 √“¬„π À√—∞Õ‡¡√‘°“ √–À«à“ßªï §.». 1996- 1997 æ∫«à“ºŸâªÉ«¬¡“°°«à“√âÕ¬≈– 50 ¡’‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥Õ¬à“ß™—¥‡®π ¬‘Ë߉ª°«à“π—Èπ À“°‡°‘¥ ‡Àμÿ°“√≥å¢Õß‚√§À—«„®¢÷Èπ„πºâŸªÉ«¬‚√§‰μ‡√◊ÈÕ√—ß√–¬–∑’Ë 5 ‚Õ°“ ∑’˺ŸâªÉ«¬®–‰¥â√—∫°“√√—°…“∑’ˇÀ¡“– ¡ ·≈–‚Õ°“ √Õ¥™’«‘μ®–μË”°«à“ºŸâ∑’ˉ¡à¡’‚√§‰μ‡√◊ÈÕ√—ß¡“°6, 7 ¥—ßπ—Èπ°“√ªÑÕß°—π‰¡à„À⇰‘¥‚√§À—«„®·≈–À≈Õ¥ ‡≈◊Õ¥‚¥¬°“√¥—¥·ª≈ߧ«“¡‡ ’ˬßμàÕ‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥„πºâŸªÉ«¬°≈ÿà¡π’È®÷ß¡’§«“¡ ”§—≠¡“°°«à“ °“√√—°…“‚√§∑’ˇ°‘¥¢÷Èπ·≈â« ‡ ¡◊Õπ‡ªìπ°“√μ—¥‰ø·μàμâπ≈¡ 2. ‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥„πºâªŸ «É ¬‚√§‰μ‡√◊ÈÕ√—ß ‚√§À—«„®„πºŸâªÉ«¬‚√§‰μ‡√◊ÈÕ√—ß·∫àßÕÕ°‡ªìπ 2 √Ÿª·∫∫„À≠àÊ §◊Õ ‚√§À≈Õ¥‡≈◊Õ¥·¢Áßμ—« (atherosclerotic disease) ‚¥¬‡©æ“–‚√§À≈Õ¥‡≈◊Õ¥À—«„® (coronary artery disease, CAD) ·≈–¿“«– °≈â“¡‡π◊ÈÕÀ—«„®º‘¥ª°μ‘ (cardiomyopathy) ´÷Ëß —¡æ—π∏å°—∫°“√‡°‘¥¿“«–À—«„®≈⡇À≈« À—«„®‡μâπº‘¥®—ßÀ«– ·≈–°“√‡ ’¬™’«‘쇩’¬∫æ≈—π 2.1 ‚√§À≈Õ¥‡≈Õ◊ ¥À—«„® ºŸâªÉ«¬‚√§‰μ‡√◊ÈÕ√—ß‚¥¬‡©æ“–„π¿“«–¬Ÿ√’‡¡’¬¡’ªí®®—¬‡ ’ˬßμàÕ°“√‡°‘¥‚√§À≈Õ¥‡≈◊Õ¥À—«„® ¡“°¡“¬ ∑—Èßªí®®—¬‡ ’ˬß∑’Ëæ∫‰¥â„πª√–™“°√∑—Ë«‰ª (traditional risk factors, Framingham) ‰¥â·°à Õ“¬ÿ¡“° ‡∫“À«“𠧫“¡¥—π‚≈À‘μ Ÿß ‰¢¡—π„π‡≈◊Õ¥º‘¥ª°μ‘ °“√ Ÿ∫∫ÿÀ√’Ë °“√‰¡àÕÕ°°”≈—ß°“¬ ·≈–Õâ«π ´÷Ëß ºªâŸ «É ¬‚√§‰μ∑‡’Ë ªπì ‡∫“À«“π¡§’ «“¡‡ ¬’Ë ßμÕà ‚√§À«— „®·≈–À≈Õ¥‡≈Õ◊ ¥¡“°°«“à º∑⟠‰’Ë ¡‡à ªπì ‡∫“À«“π∂ß÷ √Õâ ¬≈– 568 ·≈–ºªŸâ «É ¬‚√§‰μ∑√Ë’ ∫— °“√√°— …“∑¥·∑π‰μ√Õâ ¬≈– 75-85 ¡§’ «“¡¥π— ‚≈Àμ‘  ßŸ ·¡ºâ ªŸâ «É ¬‚√§‰μ®–¡ª’ ®í ®¬— ‡ ’ˬß∫“ßÕ¬à“ß≈¥≈ß ‡™àπºâŸªÉ«¬¡—°‰¡àÕâ«π  Ÿ∫∫ÿÀ√’ËπâÕ¬ ·≈–ºâŸªÉ«¬øÕ°‡≈◊Õ¥¡’√–¥—∫ cholesterol „π ‡≈◊Õ¥ ßŸ ‰¥â‰¡à∫àÕ¬ πÕ°®“°ª®í ®¬— ‡ ¬Ë’ ß∑«Ë— ‰ª·≈«â ºªâŸ «É ¬‚√§‰μ¬ß— ¡ª’ ®í ®¬— ‡ ¬Ë’ ß∑æË’ ∫‡©æ“–„π¿“«–¬√Ÿ ‡’ ¡¬’ 9 ‰¥·â °à ¿“«–‚≈À‘μ®“ß´÷Ëß∑”„ÀâÀ—«„®ÀâÕߴ⓬≈à“ß‚μ ‡¡μ–∫Õ≈‘ ¡¢Õß·§≈‡´’¬¡·≈–øÕ ‡øμº‘¥ª°μ‘ ·≈–°“√ ‡°‘¥ calcification ∑’ËÀ≈Õ¥‡≈◊Õ¥·≈–≈‘ÈπÀ—«„® ∑”„Àâ afterload  Ÿß¢÷Èπ ·≈–À≈Õ¥‡≈◊Õ¥À—«„®μ’∫≈ß ¿“«– Õ—°‡ ∫‡√◊ÈÕ√—ß ¿“«–∑ÿæ‚¿™π“°“√ hyperhomocysteinemia ·≈–°“√‡æ‘Ë¡¢÷Èπ¢Õß lipoprotein (a) ∑’Ëæ∫„π ºŸâªÉ«¬‚√§‰μ √«¡∂÷ßªí®®—¬‡ ’ˬ߄À¡àÊ ∑’Ëæ∫‡æ‘Ë¡¢÷Èπ ‰¥â·°à°“√∑”ß“π¢Õ߇´≈≈å∫ÿºπ—ßÀ≈Õ¥‡≈◊Õ¥º‘¥ª°μ‘ 144

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Practical Dialysis in the Year 2009 „πÀ«— „® ¡— æπ— ∏°å ∫— °“√‡ ¬’ ™«’ μ‘ ‡©¬’ ∫æ≈π— 11, 12 ‚¥¬æ∫«“à ºªâŸ «É ¬∑¡Ë’ æ’ ß— º¥◊ „πÀ«— „®¡“°®–¡√’ –¬–‡«≈“°“√ Õ¬àŸ√Õ¥ —Èπ°«à“ ´÷ËßÕ“®‡°‘¥®“°‡´≈≈å°≈â“¡‡π◊ÈÕÀ—«„®∂Ÿ°∑”≈“¬ À√◊Õ‡°‘¥À—«„®‡μâπº‘¥ª°μ‘ßà“¬¢÷Èπ 3. °“√ªÑÕß°—π°“√‡°‘¥‚√§À—«„®·≈–À≈Õ¥‡≈Õ◊ ¥„πºâŸª«É ¬øÕ°‡≈Õ◊ ¥ °“√ªÑÕß°—π°“√‡°‘¥‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥„πºâŸªÉ«¬øÕ°‡≈◊Õ¥À¡“¬∂÷ß°“√¥—¥·ª≈ß ªí®®—¬‡ ’ˬߢÕß‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥∑’Ë°≈à“«¡“¢â“ßμâπ „πÀ—«¢âÕπ’È®–°≈à“«∂÷ßÀ≈—°∞“π∑’Ëæ∫‡°’ˬ«°—∫ º≈¢Õß°“√°”®—¥ªí®®—¬‡ ’ˬßμàÕ‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥μàպ⟪ɫ¬øÕ°‡≈◊Õ¥ 3.1 §«“¡¥—π‚≈À‘μ Ÿß (Hypertension) ·¡®â –¡¢’ Õâ ¡≈Ÿ ®“°°“√»°÷ …“·∫∫ ß— ‡°μÀ≈“¬°“√»°÷ …“æ∫«“à §«“¡¥π— ‚≈Àμ‘  ßŸ „πºªâŸ «É ¬øÕ° ‡≈◊Õ¥ —¡æ—π∏å°—∫§«“¡‡ ’ˬßμàÕ°“√‡ ’¬™’«‘μ∑’ˇæ‘Ë¡¢÷Èπ ·μà°Á¡’À≈“¬°“√»÷°…“∑’Ëæ∫«à“§à“§«“¡¥—π systolic ·≈– diastolic ∑’ËμË”°Á —¡æ—π∏å°—∫°“√‡ ’¬™’«‘쇙àπ°—π14 ‡™◊ËÕ«à“πà“®–‡°‘¥®“°ºŸâªÉ«¬øÕ°‡≈◊Õ¥®”π«π¡“°¡’ ¿“«– cardiomyopathy ∑’Ë∑”„À⧫“¡¥—π‚≈À‘μμË”≈ß·≈–‡ ’¬™’«‘μ‡æ‘Ë¡¢÷Èπ „πªí®®ÿ∫—π¡’°“√»÷°…“‡°’ˬ«°—∫ °“√„™â¬“≈¥§«“¡¥—π‚≈À‘μ„πºŸâªÉ«¬øÕ°‡≈◊Õ¥∑’ˇªìπ·∫∫ ÿà¡·≈–¡’°“√§«∫§ÿ¡‡æ’¬ß 2 °“√»÷°…“ ‰¥â·°à FOSinopril In DIALysis (FOSIDIAL) trial15 ´ßË÷ „™â fosinopril „πºªâŸ «É ¬øÕ°‡≈Õ◊ ¥∑¡Ë’ Õ’ “¬¡ÿ “°°«“à 50 ªï ®”π«π 400 √“¬ ‡π◊ËÕß®“°¬“°≈ÿà¡ angiotensin-converting enzyme inhibitors ·≈– angiotensin receptor blockers ∂Ÿ°·π–π”„Àℙ⇪ìπ°≈ÿà¡·√°„π°“√≈¥§«“¡¥—π‚≈À‘μ¢Õߺ⟪ɫ¬øÕ°‡≈◊Õ¥ Õâ“ßÕ‘ßμ“¡¢âÕ¡Ÿ≈„πºŸâªÉ«¬ ‚√§‰μ‡√◊ÈÕ√—ß√–¬–·√°Ê ´÷Ë߬“∑—Èß 2 °≈ÿ࡙૬≈¥§«“¡‡ ’ˬßμàÕ°“√‡°‘¥‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥ ·μà°“√ »÷°…“°≈—∫æ∫«à“ fosinopril ‰¡à™à«¬≈¥‡Àμÿ°“√≥å∑“ßÀ—«„®·≈–À≈Õ¥‡≈◊Õ¥  à«πÕ’°°“√»÷°…“Àπ÷Ëßæ∫ «à“°“√„™â carvedilol ™à«¬≈¥§«“¡‡ ’ˬßμàÕ°“√‡ ’¬™’«‘μ®“°∑ÿ° “‡Àμÿ (hazard ratio, HR, 0.51) §«“¡ ‡ ¬Ë’ ßμÕà °“√‡ ¬’ ™«’ μ‘ ®“°‚√§À«— „®·≈–À≈Õ¥‡≈Õ◊ ¥ (HR 0.32) ·≈–§«“¡‡ ¬Ë’ ßμÕà °“√πÕπ‚√ß欓∫“≈ (HR 0.44) „πºŸâªÉ«¬°≈ÿ࡬àÕ¬∑’ˇªìπºŸâªÉ«¬øÕ°‡≈◊Õ¥∑’Ë¡’¿“«–À—«„®≈⡇À≈«·∫∫¡’Õ“°“√ ·≈– ejection fraction μË”°«à“√âÕ¬≈– 3516 ªí®®ÿ∫—π¬—߉¡à¡’¢âÕ¡Ÿ≈°“√»÷°…“∑’Ë„™â¬“™π‘¥Õ◊ËπÀ√◊Õ°“√§«∫§ÿ¡§«“¡¥—π‚≈À‘μ«‘∏’Õ◊Ë𠇙àπ°“√®”°—¥‡°≈◊Õ·≈–πÈ”¥◊Ë¡ μ“¡·π«ªØ‘∫—μ‘¢Õß K/DOQI ·π–π”„À⧫∫§ÿ¡§«“¡¥—π‚≈À‘μ°àÕπ·≈–À≈—ßøÕ°‡≈◊Õ¥„ÀâμË” °«à“ 140/90 ·≈– 130/80 ¡‘≈≈‘‡¡μ√ª√Õ∑μ“¡≈”¥—∫ Õâ“ßÕ‘ß®“°°“√»÷°…“ the Hypertension Optimum Treatment (HOT) study17, the Modification of Diet and Renal Disease (MDRD) study18 ·≈–°“√»÷°…“ ·∫∫ —߇°μÕ’°™‘ÈπÀπ÷Ëß∑’Ëæ∫«à“ §«“¡¥—π‚≈À‘μμË”°«à“ 140/90 ¡‘≈≈‘‡¡μ√ª√Õ∑™à«¬≈¥°“√‡°‘¥ LVH ·≈– °“√‡ ’¬™’«‘μ19 §≈⓬§≈÷ß°—∫¢âÕ·π–π”¢Õß the Caring for Australians with Renal Insuficiency (CARI) ∑’Ë ·π–π”„À⧫∫§ÿ¡§«“¡¥—π‚≈À‘μ°àÕπøÕ°‡≈◊Õ¥„ÀâμË”°«à“ 140/90 ¡‘≈≈‘‡¡μ√ª√Õ∑‡™àπ°—π °“√§«∫§ÿ¡§«“¡¥—π‚≈À‘μ∑”‰¥â‚¥¬°“√§«∫§ÿ¡πÈ”Àπ—°μ—«¢ÕߺŸâªÉ«¬„Àâ„°≈⇧’¬ßπÈ”Àπ—° ·Àâß¡“°∑’Ë ÿ¥ °“√®”°—¥‡°≈◊Õ∑—Èß®“°Õ“À“√·≈–πÈ”¬“øÕ°‡≈◊Õ¥ °“√®”°—¥πÈ”¥◊Ë¡ §«∫§ÿ¡‰¡à„ÀâπÈ”Àπ—° μ—«ºâŸªÉ«¬‡æ‘Ë¡¢÷Èπ√–À«à“ß°“√øÕ°‡≈◊Õ¥¡“°‡°‘π‰ª „™âŒÕ√å‚¡π erythropoietin Õ¬à“߇À¡“– ¡ ·π–π”„Àâ ºŸâªÉ«¬ÕÕ°°”≈—ß°“¬Õ¬à“ß ¡Ë”‡ ¡Õ ≈¥πÈ”Àπ—°À“°¡’¥—™π’¡«≈°“¬ Ÿß‡°‘π‰ª ß¥ Ÿ∫∫ÿÀ√’Ë·≈–¥◊Ë¡ ÿ√“ 146

Practical Guidelines to Reduce Cardiovascular Risk of Dialysis Patients Õ“®μâÕß∑”°“√øÕ°‡≈◊Õ¥∫àÕ¬¢÷ÈπÀ√◊Õ¬◊¥√–¬–‡«≈“„Àâπ“π¢÷Èπ ·≈–°“√„™â¬“≈¥§«“¡¥—π‚≈À‘μ´÷Ëß·π« ªØ‘∫—μ‘ K/DOQI ‰¥â·π–π”«à“¬“∑’ËÕÕ°ƒ∑∏‘Ϭ—∫¬—Èß√–∫∫ Renin-Angiotensin-Aldosterone ‰¥â·°à¬“„π°≈ÿà¡ angiotensin-converting enzyme inhibitors ·≈– angiotensin II receptor blockers ‡ªìπ¬“∑’˧«√„™â‡ªìπ°≈ÿà¡ ·√°„πºâŸªÉ«¬øÕ°‡≈◊Õ¥‡π◊ËÕß®“°™à«¬≈¥°“√‡°‘¥ LVH ≈¥°“√°√–μÿâπ¢Õß√–∫∫ª√– “∑ sympathetic ·≈–≈¥§«“¡·¢ÁߢÕßÀ≈Õ¥‡≈◊Õ¥·¥ß„πºâŸªÉ«¬‚√§‰μÕ¬à“ß™—¥‡®π πÕ°®“°π—Èπ¬—ßÕ“®∑”„ÀâÀπâ“∑’Ë¢Õß ‡´≈≈å∫ÿÀ≈Õ¥‡≈◊Õ¥¥’¢÷Èπ·≈–Õ“®™à«¬≈¥ oxidative stress ¥â«¬ 3.2 ‰¢¡π— „π‡≈◊Õ¥º¥‘ ª°μ‘ §«“¡º‘¥ª°μ‘¢Õß√–¥—∫‰¢¡—π„π‡≈◊Õ¥¢ÕߺŸâªÉ«¬øÕ°‡≈◊Õ¥¡’≈—°…≥–§≈⓬§≈÷ß°—∫ºŸâªÉ«¬‚√§ ‰μ‡√◊ÈÕ√—ß√–¬–·√°Ê ·μ৫“¡√ÿπ·√ßÕ“®πâÕ¬°«à“‡¡◊ËÕ∑”°“√øÕ°‡≈◊Õ¥‰ª‡ªìπ‡«≈“π“π °≈à“«§◊ÕºŸâªÉ«¬  à«π„À≠à¡—°¡’√–¥—∫ triglyceride ‡æ‘Ë¡¢÷Èπ total cholesterol ·≈– low-density lipoprotein (LDL) Õ“®®– ª°μÀ‘ √Õ◊ ‡æ¡Ë‘ ¢πÈ÷ °‰Á ¥â intermediate-density lipoprotein (IDL) ·≈– very low-density lipoprotein (VLDL) ‡æ¡Ë‘ ¢πÈ÷  à«π high-density lipoprotein (HDL) ≈¥≈ß ´÷Ëß≈â«π‡Õ◊ÈÕμàÕ°“√‡°‘¥¿“«–À≈Õ¥‡≈◊Õ¥·¢Áßμ—« ¬“°≈ÿà¡ statins ‡ªìπ¬“∑’Ë¡’ª√– ‘∑∏‘¿“æ„π°“√≈¥√–¥—∫ cholesterol ·≈–¡’§«“¡ª≈Õ¥¿—¬ „πºŸâªÉ«¬‚√§‰μ ·≈–¬—ß¡’¢âÕ¡Ÿ≈«à“™à«¬≈¥Õÿ∫—μ‘°“√≥å¢Õ߇Àμÿ°“√≥å∑“ßÀ—«„®·≈–À≈Õ¥‡≈◊Õ¥„π ª√–™“°√ª°μ‘·≈–ºŸâªÉ«¬‡∫“À«“π™π‘¥∑’Ë 2 ·μàº≈∑’ˉ¥â®“°°“√»÷°…“·∫∫ ÿà¡·≈–¡’°“√§«∫§ÿ¡„πºŸâªÉ«¬ øÕ°‡≈◊Õ¥‡æ’¬ß°“√»÷°…“‡¥’¬«§◊Õ the German Die Deutsche Diabetes Dialyse (4D) study20 ∑’Ë»÷°…“°“√ „™¬â “ atorvastatin ¢π“¥ 20 ¡≈‘ ≈°‘ √¡— /«π— „πºªâŸ «É ¬‡∫“À«“π∑∑’Ë ”°“√øÕ°‡≈Õ◊ ¥ 1255 √“¬ æ∫«“à atorvastatin  “¡“√∂≈¥√–¥—∫ LDL ≈߉¥â√âÕ¬≈– 42 ¿“¬„π 4  —ª¥“Àå·√° ·μà°≈—∫‰¡à≈¥§«“¡‡ ’ˬßμàÕ°“√‡ ’¬™’«‘μ ®“°‚√§À«— „®·≈–À≈Õ¥‡≈Õ◊ ¥ °“√‡°¥‘ °≈“â ¡‡πÕÈ◊ À«— „®μ“¬∑‰Ë’ ¡‡à  ¬’ ™«’ μ‘ ·≈–°“√‡°¥‘ ‚√§À≈Õ¥‡≈Õ◊ ¥ ¡Õß Õ¬à“߉√°Á¥’°“√»÷°…“ÕÕ°·∫∫¡“‡æ◊ËÕμ√«®§«“¡·μ°μà“ß√âÕ¬≈– 27 ¢Õß primary end point ¥—ßπ—ÈπÕ“® ‡ªìπ‰ª‰¥â«à“ atorvastatin ¡’ª√–‚¬™πå„π —¥ à«π∑’ËπâÕ¬°«à“√âÕ¬≈– 27 À√◊ÕÕ“®æ∫ª√–‚¬™π宓°°“√„™â ¬“¢π“¥ Ÿß¢÷Èπ ºŸâ«‘®—¬ √ÿª«à“‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥„πºŸâªÉ«¬øÕ°‡≈◊Õ¥Õ“®Õ¬Ÿà„π√–¬–√ÿπ·√ß·≈–Õ“® ‡√‘Ë¡„Àâ statins ™â“‡°‘π‰ª ªí®®ÿ∫—π¬—ß¡’°“√»÷°…“·∫∫ ÿࡇ°’ˬ«°—∫°“√„™â statins „πºŸâªÉ«¬‚√§‰μ‡√◊ÈÕ√—ß √–¬–·√°Ê Õ’°À≈“¬°“√»÷°…“∑’ˬ—߉¡à‡ √Á® ‘È𠇙àπ the Studies of Heart and Renal Protection (SHARP) ·≈– the Study to evaluate the Use of Rosuvastatin in subjects On Regular hemodialysis: an Assessment of survival and cardiovascular events (AURORA) ´÷ËßμâÕßμ‘¥μ“¡º≈°“√»÷°…“μàÕ‰ª ·¡„â πºªŸâ «É ¬øÕ°‡≈Õ◊ ¥®–æ∫«“à ¡√’ –¥∫— triglyceride „π‡≈Õ◊ ¥ ßŸ ‰¥∫â Õà ¬°«“à cholesterol „π‡≈Õ◊ ¥  ßŸ ·μ°à ¬Á ß— ‰¡∑à √“∫·π™à ¥— ∂ß÷ ª√–‚¬™π¢å Õß°“√„™¬â “‡æÕË◊ ≈¥√–¥∫— triglyceride „π‡≈Õ◊ ¥¢ÕߺªâŸ «É ¬øÕ°‡≈Õ◊ ¥ ·¡â®–¡’¢âÕ¡≈Ÿ ®“° the Veteransû Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) «à“°“√„™â gemfibrozil ¢π“¥ 1200 ¡‘≈≈‘°√—¡/«—π ®–≈¥°“√‡ ’¬™’«‘μ®“°‚√§À≈Õ¥‡≈◊Õ¥À—«„®À√◊Õ°“√‡°‘¥°≈â“¡‡π◊ÈÕ À—«„®μ“¬∑’ˉ¡à‡ ’¬™’«‘μ≈ß√âÕ¬≈– 27 „πºâŸªÉ«¬‚√§À≈Õ¥‡≈◊Õ¥À—«„® ∑’ˇªìπ‡æ»™“¬ ¡’‰¢¡—π„π‡≈◊Õ¥ Ÿß ·≈–¡‰’ μ‡ ÕË◊ ¡‡≈°Á πÕâ ¬∂ß÷ ª“π°≈“ß (GFR μ”Ë °«“à 75 ¡≈‘ ≈≈‘ μ‘ √/π“∑)’ 21 ·μ°à ¬Á ß— ‰¡¡à ¢’ Õâ ¡≈Ÿ ¥ß— °≈“à «„πºªâŸ «É ¬ ‚√§‰μ‡√◊ÈÕ√—ß√–¬–∑’Ë 4 ·≈– 5 μ“¡·π«ªØ‘∫—μ‘¢Õß K/DOQI ·≈– CARI ®—¥ºŸâªÉ«¬‚√§‰μ‡√◊ÈÕ√—߇ªìπºâŸ¡’§«“¡‡ ’ˬߠߟ ∑’Ë ÿ¥μàÕ 147

Practical Dialysis in the Year 2009 °“√‡°‘¥‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥ ®÷ß·π–π”„À⧫∫§ÿ¡√–¥—∫ LDL „ÀâπâÕ¬°«à“ 100 ¡‘≈≈‘°√—¡/‡¥´‘≈‘μ√ ‚¥¬ºŸâªÉ«¬∫“ß√“¬Õ“®μâÕß°“√‡æ’¬ß·§à°“√ª√—∫‡ª≈’ˬπ√Ÿª·∫∫°“√¥”‡π‘π™’«‘μ°Á‡æ’¬ßæÕ ‰¥â·°à°“√ ‡ª≈¬’Ë π·ª≈ß ¥—  «à πÕ“À“√‚¥¬≈¥ª√¡‘ “≥ cholesterol (μË”°«“à 200 ¡≈‘ ≈°‘ √¡— /«π— ) ·≈–ª√¡‘ “≥‰¢¡π— Õ¡‘Ë μ«— æ≈—ßß“π®“° “√Õ“À“√§“√å‚∫‰Œ‡¥√집¥‡ªìπ√âÕ¬≈– 50-60 ¢Õߧ«“¡μâÕß°“√æ≈—ßß“π„π·μà≈–«—π °“° „¬Õ“À“√ 20-30 °√—¡/«—𠧫∫§ÿ¡√–¥—∫πÈ”μ“≈„π‡≈◊Õ¥·≈–§«∫§ÿ¡πÈ”Àπ—°μ—«„ÀâÕ¬àŸ„π‡°≥±åª°μ‘ πÕ°®“°π—Èπ¬—ß„Àâ¡’°‘®°√√¡∑“ß°“¬ª“π°≈“ß ¥◊Ë¡‡§√◊ËÕߥ◊Ë¡·Õ≈°ÕŒÕ≈åª√‘¡“≥πâÕ¬Ê ·≈–À¬ÿ¥ Ÿ∫∫ÿÀ√’Ë ·μàºâŸªÉ«¬ à«π„À≠à®”‡ªìπμâÕß„™â¬“‡æ◊ËÕ§«∫§ÿ¡√–¥—∫ cholesterol „À≥âμ“¡‡ªÑ“À¡“¬‚¥¬¬“°≈ÿà¡·√°∑’Ë ·π–π”„π°“√≈¥√–¥—∫ LDL §◊Õ¬“°≈ÿà¡ statins ‚¥¬Õâ“ßÕ‘ß®“°¢âÕ¡Ÿ≈„πºâŸªÉ«¬‚√§‰μ‡√◊ÈÕ√—ß√–¬–·√°Ê ·≈–„πª√–™“°√∑—Ë«‰ª πÕ°®“°π—Èπ¬—ßμâÕߧ«∫§ÿ¡√–¥—∫ triglyceride „ÀâμË”°«à“ 500 ¡‘≈≈‘°√—¡/‡¥´‘≈‘μ√ ·≈– non-HDL cholesterol (· ¥ß∂÷ß VLDL ·≈– IDL) „ÀâμË”°«à“ 130 ¡‘≈≈‘°√—¡/‡¥´‘≈‘μ√ ‚¥¬·π–π”„Àℙ⠬“°≈ÿà¡ fibrate (‚¥¬‡©æ“– gemfibrozil) ‡¡◊ËÕ√–¥—∫ triglyceride  ßŸ °«à“ 500 ·≈–‡√‘Ë¡∑”°“√§«∫§ÿ¡√–¥—∫ ‰¢¡—π„π‡≈◊Õ¥μ—Èß·μà„π√–¬–·√°¢Õß‚√§‰μ‡√◊ÈÕ√—ß 3.3 ¿“«–¥◊ÈÕÕπ‘  ÿ≈π‘ (Insulin resistance), ‡∫“À«“π (Diabetes) ·≈–°“√§«∫§¡ÿ √–¥∫— π”È μ“≈ ‡∫“À«“π‡ªπì ª®í ®¬— ‡ ¬Ë’ ßÕ ‘ √–¢Õß‚√§À«— „®¢“¥‡≈Õ◊ ¥ À«— „®≈¡â ‡À≈« ·≈–°“√‡ ¬’ ™«’ μ‘ ®“°∑°ÿ  “‡Àμÿ„πºŸâªÉ«¬øÕ°‡≈◊Õ¥22 ªí®®ÿ∫—π¬—߉¡à¡’¢âÕ¡≈Ÿ ®“°°“√»÷°…“·∫∫ ÿà¡·≈–¡’°“√§«∫§ÿ¡∂÷ߺ≈¢Õß°“√ §«∫§ÿ¡√–¥—∫πÈ”μ“≈„πºŸâªÉ«¬‚√§‰μ‡√◊ÈÕ√—ß√–¬–∑’Ë 5 Õ¬à“߉√°Á¥’®“°°“√»÷°…“ the United Kingdom Prospective Diabetes Study (UKPDS) ·≈– the Diabetes Control and Complications Trial (DCCT) æ∫«à“ °“√§«∫§ÿ¡πÈ”μ“≈Õ¬à“߇§√àߧ√—¥¡’º≈™à«¬≈¥¿“«–·∑√°´âÕπ∑“ßÀ≈Õ¥‡≈◊Õ¥¢π“¥‡≈Á° ·μà‰¡à≈¥¿“«– ·∑√°´âÕπ∑“ßÀ≈Õ¥‡≈◊Õ¥¢π“¥„À≠à„πºŸâªÉ«¬‡∫“À«“π23-25 ¿“«–¥Õ◊È Õπ‘  ≈ÿ π‘ æ∫‰¥∫â Õà ¬„πºªâŸ «É ¬‚√§‰μ‡√Õ◊È √ß— ·≈–æ∫‰¥μâ ß—È ·μ„à π√–¬–·√°Ê26 ¿“«–¥Õ◊È Õπ‘  ÿ≈‘π¡—°æ∫√à«¡°—∫ªí®®—¬‡ ’ˬßÕ◊ËπÊ ¢Õß‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥ πÕ°®“°π—Èπ¬—ß¡’¢âÕ¡Ÿ≈„πºŸâªÉ«¬øÕ° ‡≈◊Õ¥«à“¿“«–¥◊ÈÕÕ‘π ÿ≈‘π∑”„À⇡μ–∫Õ≈‘ ¡¢Õß°√¥‰¢¡—π„πÀ—«„®º‘¥ª°μ‘´÷ËßÕ“®∑”„Àâ°“√∑”ß“π¢Õß À—«„®ÀâÕߴ⓬≈à“ߺ‘¥ª°μ2‘ 7 °“√·°â‰¢¿“«–¥◊ÈÕÕ‘π ÿ≈‘πÕ“®∑”‰¥â‚¥¬°“√„™â¬“ angiotensin converting-enzyme inhibitors ·≈– thiazolidinediones28 ·π«ªØ‘∫—μ‘¢Õß K/DOQI ·≈– CARI ‡°’ˬ«°—∫°“√§«∫§ÿ¡√–¥—∫πÈ”μ“≈„π‡≈◊Õ¥ ·π–π”„Àâ∑”μ“¡·π«ªØ‘∫—μ‘¢Õß ¡“§¡‚√§‡∫“À«“π‚¥¬∑—Ë«‰ª 3.4 ‚≈À‘μ®“ß (Anemia) ¡’°“√»÷°…“·∫∫ —߇°μ®”π«πÀπ÷Ëß√“¬ß“π«à“ √–¥—∫Œ’‚¡‚°≈∫‘π∑’ËμË”≈ß„πºŸâªÉ«¬øÕ°‡≈◊Õ¥  —¡æ—π∏å°—∫°“√‡ ’¬™’«‘μ∑’ˇæ‘Ë¡¢÷Èπ Õ¬à“߉√°Á¥’ „πªí®®ÿ∫—π¬—߉¡à¡’¢âÕ¡Ÿ≈«à“°“√‡æ‘Ë¡Œ’‚¡‚°≈∫‘π¢÷Èπ¡“„Àâ∂÷ß √–¥—∫ª°μ‘®–¡’ª√–‚¬™πå ®“°°“√»÷°…“ the United States Normal Hematocrit Trial29 ´÷Ëß»÷°…“‚¥¬°“√  ÿࡺŸâªÉ«¬øÕ°‡≈◊Õ¥∑’Ë¡’¿“«–À—«„®≈⡇À≈«À√◊Õ‚√§À—«„®¢“¥‡≈◊Õ¥ 1233 √“¬ ÕÕ°‡ªìπ Õß°≈ÿà¡∑’Ë¡’ √–¥—∫Œ’¡“‚μ§√‘μ‡ªÑ“À¡“¬∑’Ë√âÕ¬≈– 30 ·≈– 42 °“√»÷°…“μâÕß ‘Èπ ÿ¥°àÕπ°”Àπ¥ ‡π◊ËÕß®“°°≈ÿà¡∑’Ë Œ’¡“‚μ§√‘μ Ÿß°«à“¡’·π«‚πâ¡∑’Ë®–¡’°“√‡ ’¬™’«‘μ ·≈–‡°‘¥°≈â“¡‡π◊ÈÕÀ—«„®μ“¬∑’ˉ¡à‡ ’¬™’«‘μ§√—Èß·√°¡“° 148

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Practical Dialysis in the Year 2009 ®“°°“√μ√«®¥â«¬ electron beam tomography44  à«π°“√»÷°…“ the Dialysis Clinical Outcomes Revisited (DCOR) study √“¬ß“π«à“ ‡¡◊ËÕμ‘¥μ“¡ºŸâªÉ«¬ 2100 √“¬‰ª‡ªìπ‡«≈“ 3 ªï ‰¡à¡’§«“¡·μ°μà“ߢÕߧ«“¡ ‡ ’ˬßμàÕ°“√‡ ’¬™’«‘μ√–À«à“ߺâŸ∑’ˉ¥â√—∫ sevelamer ·≈–ºŸâ∑’ˉ¥â√—∫ “√®—∫øÕ ‡øμ∑’Ë¡’·§≈‡´’¬¡‡ªìπ à«π ª√–°Õ∫ ·μà‡¡◊ËÕ∑”°“√«‘‡§√“–Àå¬àÕ¬®–æ∫ª√–‚¬™πå¢Õß sevelamer „π°≈ÿà¡∑’ˉ¥â√—∫¬“¡“Õ¬à“ßπâÕ¬ 2 ªï À√◊ÕºâŸ∑’Ë¡’Õ“¬ÿ¡“°°«à“ 65 ªï Cunningham ·≈–§≥–45 ‰¥∑â ”°“√«‡‘ §√“–À¢å Õâ ¡≈Ÿ ®“°°“√»°÷ …“·∫∫ ¡ÿà 4 °“√»°÷ …“∑‡’Ë ª√¬’ ∫ ‡∑’¬∫°“√„™â cinacalcet (697 √“¬) ‡∑’¬∫°—∫¬“À≈Õ° (487 √“¬) „πºŸâªÉ«¬‚√§‰μ‡√◊ÈÕ√—ß√–¬–∑’Ë 5 ∑’Ë¡’¿“«– secondary hyperparathyroidism ∑’˧«∫§ÿ¡‰¡à‰¥â (intact parathyroid hormone Õ¬à“ßπâÕ¬ 300 æ‘‚§°√—¡/ ¡‘≈≈‘≈‘μ√) æ∫«à“ºŸâ∑’ˉ¥â√—∫ cinacalcet ¡’§«“¡‡ ’ˬßμàÕ°“√‡¢â“√—∫°“√√—°…“„π‚√ß欓∫“≈®“°‚√§À—«„® ·≈–À≈Õ¥‡≈◊Õ¥≈¥≈ß (RR 0.61, 95% CI 0.43-0.86) ·π«ªØ‘∫—μ‘¢Õß K/DOQI ·≈– CARI ·π–π”„À⧫∫§ÿ¡√–¥—∫øÕ ‡øμ ·§≈‡´’¬¡ æ“√“ ∏—¬√Õ¬¥åŒÕ√å‚¡π„À≥âμ“¡‡°≥±å∑’Ë°”À𥉫âμ“¡√–¬–μà“ßÊ ¢Õß‚√§‰μ‡√◊ÈÕ√—ß ·≈–‡¡◊ËÕ∂÷ß√–¬–∑’ËμâÕß ∑”°“√øÕ°‡≈Õ◊ ¥ „À§â «∫§¡ÿ √–¥∫— øÕ ‡øμ„π‡≈Õ◊ ¥‡∑“à °∫— 3.5-5.5 ¡≈‘ ≈°‘ √¡— /‡¥´≈‘ μ‘ √ √–¥∫— ·§≈‡´¬’ ¡ 8.4- 9.5 ¡≈‘ ≈°‘ √¡— /‡¥´≈‘ μ‘ √ º≈§≥Ÿ ¢Õß·§≈‡´¬’ ¡·≈–øÕ ‡øμ‰¡‡à °π‘ 55 ·≈–æ“√“∏¬— √Õ¬¥Œå Õ√‚å ¡π‡∑“à °∫— 150- 300 æ‘‚§°√—¡/¡‘≈≈‘≈‘μ√ ‚¥¬μâÕß∑”°“√«—¥√–¥—∫øÕ ‡øμ·≈–·§≈‡´’¬¡∑ÿ° 1 ‡¥◊Õπ ·≈–«—¥√–¥—∫æ“√“ ∏—¬√Õ¬¥åŒÕ√å‚¡π∑ÿ° 3 ‡¥◊Õπ ·≈–„Àâ°“√√—°…“´÷Ëߪ√–°Õ∫¥â«¬ 3.5.1 °“√®”°—¥ª√‘¡“≥øÕ ‡øμ„πÕ“À“√‡À≈◊Õ 600-900 ¡‘≈≈‘°√—¡/«—π 3.5.2 °“√„™â “√¥—°®—∫øÕ ‡øμ„π∑“߇¥‘πÕ“À“√‡æ◊ËÕ≈¥°“√¥¥Ÿ ´÷¡ ‰¥â·°à - ‡°≈◊Õ·§≈‡´’¬¡´÷Ëß„Àâ„™â elemental calcium ‰¡à‡°‘π 2000 ¡‘≈≈‘°√—¡/«—π ‡æ◊ËÕªÑÕß°—π°“√μ° μ–°Õπ¢Õ߇°≈◊Õ·§≈‡´’¬¡ ·≈–°“√°¥°“√∑”ß“π¢ÕßμàÕ¡æ“√“∏—¬√Õ¬¥å¡“°‡°‘π‰ª -  “√ª√–°Õ∫Õ–≈Ÿ¡‘π—¡ Õ“®∑”„À⇰‘¥°“√ – ¡¢ÕßÕ–≈Ÿ¡‘π—¡„π√à“ß°“¬∑”„À⇰‘¥‚√§  ¡Õ߇ ◊ËÕ¡ °√–¥Ÿ°∫“ß °≈â“¡‡π◊ÈÕÕàÕπ·√ß ·≈–´’¥ ®÷ßÕπÿ‚≈¡„Àℙ⇩擖‡¡◊ËÕ√–¥—∫øÕ ‡øμ„π‡≈◊Õ¥ Ÿß ¡“°°«à“ 7 ¡‘≈≈‘°√—¡/‡¥´‘≈‘μ√ ·≈–„™âμ‘¥μàÕ°—π‰¡à‡°‘π 4  —ª¥“Àå -  “√¥°— ®∫— øÕ ‡øμ„π∑“߇¥π‘ Õ“À“√μ«— Õπ◊Ë Ê ‰¥·â °à polyallylamine hydrochrolide (sevelamer) ·≈– lanthanum carbonate 3.5.3 °“√§«∫§ÿ¡√–¥—∫æ“√“∏—¬√Õ¬¥åŒÕ√å‚¡π - °“√„™â«‘μ“¡‘π¥’À√◊Õ¬“∑’ËÕÕ°ƒ∑∏‘χ ¡◊Õπ«‘μ“¡‘π¥’ ‚¥¬·π–π”„Àâ„™â„π√Ÿª¢Õß°“√©’¥‡¢â“ À≈Õ¥‡≈◊Õ¥‡ªìπ√–¬–Ê ®–‰¥âº≈¡“°°«à“°“√√—∫ª√–∑“π - °“√„™â¬“‡æ‘Ë¡§«“¡‰«¢Õß CaSR μàÕ√–¥—∫·§≈‡´’¬¡πÕ°‡´≈≈å (calcimimetics) - °“√ºà“μ—¥≈¥®”π«πæ“√“∏—¬√Õ¬¥å‡´≈≈å ‰¥â·°à°“√ºà“μ—¥μàÕ¡æ“√“∏—¬√Õ¬¥åÕÕ° °“√©’¥ ·Õ≈°ÕŒÕ≈凢Ⓣª„πμàÕ¡æ“√“∏—¬√Õ¬¥å‡æ◊ËÕ∑”≈“¬‡´≈≈åæ“√“∏—¬√Õ¬¥å À√◊Õ°“√©’¥μàÕ¡æ“√“∏—¬√Õ¬¥å ¥â«¬«‘μ“¡‘π¥’ ¬“‡ ¡◊Õπ«‘μ“¡‘π¥’ À√◊Õ calcimimetics ·π–π”„Àâ∑”°“√ºà“μ—¥μàÕ¡æ“√“∏—¬√Õ¬¥åÕÕ° ‡¡◊ËÕ√–¥—∫æ“√“∏—¬√Õ¬¥åŒÕ√å‚¡π Ÿß°«à“ 800 æ‘‚§°√—¡/¡‘≈≈‘≈‘μ√ √à«¡°—∫¡’√–¥—∫·§≈‡´’¬¡À√◊ÕøÕ ‡øμ „π‡≈Õ◊ ¥ ßŸ ·≈–‰¡μà Õ∫ πÕßμÕà °“√√°— …“¥«â ¬¬“ À√Õ◊ Õ“®∑”∂“â √–¥∫— æ“√“∏¬— √Õ¬¥Œå Õ√‚å ¡π‡°π‘ °«“à 500 æ‘‚§°√—¡/¡‘≈≈‘≈‘μ√ √à«¡°—∫ºâŸªÉ«¬¡’¿“«– calciphylaxis 150

Practical Guidelines to Reduce Cardiovascular Risk of Dialysis Patients 3.5.4 °“√æ—≤π“‡∑§π‘§°“√øÕ°‡≈◊Õ¥ ‰¥â·°à°“√øÕ°‡≈◊Õ¥„Àâπ“π¢÷Èπ (extended dialysis) ·≈–°“√‡æ‘Ë¡ convective therapy ‡™àπ°“√∑” high-flux dialysis À√◊Õ hemodiafiltration 3.6 Hyperhomocysteinemia Homocysteine ‡ªìπ°√¥Õ–¡‘‚π∑’Ë¡’´—≈‡øÕ√å ·≈–®“°°“√∑¥≈Õßæ∫«à“‡ªìπæ‘…μàÕÀ≈Õ¥‡≈◊Õ¥ √–¥—∫¢Õß homocysteine „π‡≈◊Õ¥¢ÕߺŸâªÉ«¬‚√§‰μ‡√◊ÈÕ√—߇æ‘Ë¡¢÷Èπμ—Èß·μà√–¬–·√°¢Õß‚√§ ·≈–®–‡æ‘Ë¡¢÷Èπ „πºŸâªÉ«¬‰μ«“¬‡√◊ÈÕ√—ß√–¬– ÿ¥∑⓬‡°◊Õ∫∑ÿ°√“¬ ‚¥¬æ∫«à“°“√‡æË‘¡¢÷Èπ —¡æ—π∏å°—∫Õ—μ√“°“√‡ ’¬™’«‘μ®“° ‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥∑’ˇæ‘Ë¡¢÷Èπ∑—Èß„πºŸâªÉ«¬øÕ°‡≈◊Õ¥·≈–ºâŸªÉ«¬≈â“߉μ∑“ß™àÕß∑âÕß46, 47 „π¢≥–∑’ËÕ’° À≈“¬°“√»÷°…“æ∫«à“√–¥—∫ homocysteine √«¡„π‡≈◊Õ¥¡’§«“¡ —¡æ—π∏å·∫∫º°º—πÀ√◊Õ‰¡àæ∫«à“¡’§«“¡  —¡æ—π∏å°—∫°“√‡ ’¬™’«‘μ®“°‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥47-49 Õ¬à“߉√°Á¥’ homocysteine „π°√–· ‡≈◊Õ¥®– ®—∫°—∫Õ—≈∫Ÿ¡‘π ¥—ßπ—È𧫓¡ —¡æ—π∏å·∫∫º°º—π¥—ß°≈à“«Õ“®‡ªìπº≈¡“®“°¿“«–°“√Õ—°‡ ∫ ·≈–∑ÿæ ‚¿™π“°“√´÷Ëß∑”„Àâ√–¥—∫Õ—≈∫Ÿ¡‘π„π‡≈◊Õ¥μË”≈ß·≈–∑”„Àâ°“√‡ ’¬™’«‘μ¡“°¢÷Èπ50, 51 ¡’°“√»÷°…“„πºâŸªÉ«¬ øÕ°‡≈◊Õ¥∑’ˉ¡à¡’Õ“°“√· ¥ß¢Õß°“√Õ—°‡ ∫·≈–∑ÿæ‚¿™π“°“√ æ∫«à“√–¥—∫¢Õß homocysteine ∑’ˇæ‘Ë¡ ¢÷Èπ‡ªìπμ—«∑”π“¬∑’Ë¥’∂÷ß°“√‡ ’¬™’«‘μ®“°∑ÿ° “‡Àμÿ ·≈–®“°‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥52 °“√√—∫ª√–∑“π folic acid, vitamin B12, pyridoxine ·≈– acetylcysteine ™à«¬≈¥√–¥—∫ homocysteine„πºªâŸ «É ¬‰μ«“¬‡√Õ◊È √ß— ·≈–ºªâŸ «É ¬≈“â ߉μ∑“ß™Õà ß∑Õâ ß≈߉¥5â 3-55·μ¬à ß— ¢“¥°“√»°÷ …“∂ß÷ º≈≈æ— ∏å ¢Õß°“√≈¥√–¥—∫ homocysteine ≈ß ¡’°“√»÷°…“·∫∫ ÿà¡·≈–¡’°“√§«∫§ÿ¡‡æ’¬ß°“√»÷°…“‡¥’¬« ∑”‚¥¬ „Àâ folic acid „π¢π“¥ 1, 5 ·≈– 15 ¡‘≈≈‘°√—¡/«—π ·°àºŸâªÉ«¬ 510 √“¬ (øÕ°‡≈◊Õ¥√âÕ¬≈– 82, ≈â“߉μ∑“ß ™àÕß∑âÕß√âÕ¬≈– 18) æ∫«à“√–¥—∫ homocysteine √«¡≈¥≈ßÕ¬à“ß¡’π—¬ ”§—≠μ“¡¢π“¥¢Õß folic acid ∑’Ë ‰¥â√—∫ ·μàÕ—μ√“°“√‡ ’¬™’«‘μ·≈–‡Àμÿ°“√≥å∑“ßÀ—«„®·≈–À≈Õ¥‡≈◊Õ¥„πºŸâªÉ«¬∑—Èß 3 °≈ÿࡉ¡à·μ°μà“ß°—π48 πÕ°®“°π—Èπ¡’°“√»÷°…“æ∫«à“ °“√‡ª≈’ˬπ·ª≈ߢÕß MTHFR gene  —¡æ—π∏å°—∫°“√‡ ’¬™’«‘μ¢ÕߺŸâªÉ«¬ øÕ°‡≈◊Õ¥∑’Ë¡’ homocysteine  ßŸ 46 ·≈–°“√»÷°…“ the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) °Á„Àºâ ≈≈æ— ∏å§≈“â ¬°—π „πªí®®∫ÿ —π®ß÷ ¬—ß¡’¢Õâ ¡≈Ÿ ‰¡‡à æ’¬ßæÕ∑’®Ë –·π–𔇰’ˬ«°—∫°“√μ√«®À“ ·≈–°“√√—°…“¿“«– hyperhomocysteinemia 3.7 °“√øÕ°‡≈Õ◊ ¥‰¡à‡æ’¬ßæÕ ¡’°“√»÷°…“·∫∫ observational cohort À≈“¬°“√»÷°…“· ¥ß„Àâ‡ÀÁπ«à“Õ—μ√“°“√‡ ’¬™’«‘μ ·≈–∑ÿææ≈¿“æ≈¥≈ßÕ¬à“ß¡’π—¬ ”§—≠‡¡◊ËÕ‡æ‘Ë¡¢π“¥¢Õß°“√øÕ°‡≈◊Õ¥„Àâ·°àºâŸªÉ«¬56-58 Õ¬à“߉√°Á¥’®“° °“√»÷°…“·∫∫ ÿà¡·≈–¡’°“√§«∫§ÿ¡ 2 °“√»÷°…“§◊Õ the National Co-operative Dialysis Study (NCDS) 59 ´÷Ëß»÷°…“„πºŸâªÉ«¬ 151 √“¬ ·≈– the Hemodialysis (HEMO) study60 ´÷Ëß»÷°…“„πºâŸªÉ«¬∑’ËøÕ°‡≈◊Õ¥¡“ π“π°«à“ 3 ‡¥◊Õπ 1846 √“¬ °≈—∫‰¡àæ∫«à“¢π“¥¢Õß°“√øÕ°‡≈◊Õ¥∑’ˇæ‘Ë¡¢÷Èπ —¡æ—π∏å°—∫Õ—μ√“°“√‡ ’¬ ™’«‘μ∑’Ë≈¥≈ß ·¡â„π HEMO study ‡¡◊ËÕ¡“∑”°“√«‘‡§√“–Àå°≈ÿ࡬àÕ¬®–æ∫«à“°“√„™âμ—«°√Õß high-flux ‡¡◊ËÕ ‡∑’¬∫°—∫°“√„™âμ—«°√Õß low-flux ®–¡’°“√‡ ’¬™’«‘μ®“°‚√§À—«„® °“√‡ ’¬™’«‘μ®“°‚√§À≈Õ¥‡≈◊Õ¥ ¡Õß ·≈–°“√πÕπ‚√ß欓∫“≈§√—Èß·√°μË”°«à“„π°≈ÿࡺŸâªÉ«¬∑’ËøÕ°‡≈◊Õ¥¡“π“π°«à“ 3.7 ªï °àÕπ®–‡¢â“√à«¡ °“√»÷°…“ 151

Practical Dialysis in the Year 2009 ¡’°“√»÷°…“‡≈Á°Ê Õ’°®”π«πÀπ÷Ëß∑’Ëæ∫«à“°“√øÕ°‡≈◊Õ¥∂’Ë¢÷È𠇙àπ°“√øÕ°‡≈◊Õ¥μÕπ°≈“ߧ◊π À√◊Õ°“√øÕ°‡≈◊Õ¥ —ÈπÊ „πμÕπ°≈“ß«—π Õ“® —¡æ—π∏å°—∫º≈≈—æ∏å∑“ßÀ—«„®À≈Õ¥‡≈◊Õ¥∑’Ë¥’¢÷Èπ61-65 ·μàÀ≈—° ∞“π¥—ß°≈à“«¬—߉¡à‡¢â¡·¢ÁßæÕ∑’Ë®–π”°“√øÕ°‡≈◊Õ¥·∫∫π’È¡“„™â‡ªìπ·π«ªØ‘∫—쑉¥â 3.8 ¿“«–∑æÿ ‚¿™π“°“√ ¿“«–∑ÿæ‚¿™π“°“√‡ªìπμ—«∑”π“¬∑’Ë¥’∂÷ß°“√‡ ’¬™’«‘μ®“°∑ÿ° “‡Àμÿ·≈–®“°‚√§À—«„®·≈– À≈Õ¥‡≈◊Õ¥„πºâŸªÉ«¬∑’ˉ¥â√—∫°“√√—°…“∑¥·∑π‰μ66, 67 Õ“®Õ∏‘∫“¬‰¥â®“°§«“¡ —¡æ—π∏å√–À«à“ß¿“«–∑ÿæ ‚¿™π“°“√ °“√Õ—°‡ ∫ ·≈–À≈Õ¥‡≈◊Õ¥·¢Áßμ—« (Malnutrition-Inflammation-Atherosclerosis syndrome)68 ª®í ®∫ÿ π— ¬ß— ‰¡¡à ¢’ Õâ ¡≈Ÿ «“à °“√·°‰â ¢¿“«–∑æÿ ‚¿™π“°“√®–≈¥§«“¡‡ ¬’Ë ßμÕà °“√‡°¥‘ ‚√§À«— „®·≈–À≈Õ¥‡≈Õ◊ ¥ „π∑“ߪؑ∫—μ‘ ºâŸªÉ«¬∑ÿ°√“¬μâÕ߉¥â√—∫§”ª√÷°…“∑“ߥâ“π‚¿™π“°“√μ—Èß·μà·√°‡¢â“√—∫°“√øÕ°‡≈◊Õ¥ ‡æ◊ËÕ „Àâ∑√“∫∂÷ß°“√‡ª≈’ˬπ·ª≈ß„π°“√∫√‘‚¿§Õ“À“√ ·≈–®–μâÕß¡’°“√«“ß·ºπ°“√„Àâ‚¿™π∫”∫—¥∑’ˇÀ¡“–  ¡°—∫ºŸâªÉ«¬·μà≈–√“¬ ·æ∑¬å·≈–∫ÿ§§≈“°√μâÕßÀ¡—Ëπμ‘¥μ“¡¿“«–∑“ß‚¿™π“°“√¢ÕߺŸâªÉ«¬ ‚¥¬‡√‘Ë¡ μ√«®‡¡ÕË◊ ºªâŸ «É ¬‡√¡Ë‘ ‰¥√â ∫— °“√øÕ°‡≈Õ◊ ¥·≈–쥑 μ“¡∑°ÿ 3-6 ‡¥Õ◊ π À“°¡°’ “√‡ª≈¬Ë’ π·ª≈߉ª„π∑“ß∑·Ë’ ¬≈à ß „Àâ√’∫À“ “‡Àμÿ·≈–„Àâ‚¿™π∫”∫—¥·μà‡π‘Ëπ ªí®®ÿ∫—π¬—ß¡’ªí≠À“°“√¢“¥μ—«™’È«—¥¿“«–‚¿™π“°“√∑’Ëμ√«®‰¥â ßà“¬ ∑”‰¥â·æ√àÀ≈“¬ ·≈–‡™◊ËÕ∂◊Õ‰¥â 3.9 °“√Õ—°‡ ∫ ¿“«–°“√Õ—°‡ ∫‡√◊ÈÕ√—߇ªìπμ—«‡√àß„À⇰‘¥À≈Õ¥‡≈◊Õ¥·¢Áßμ—« ‚¥¬∑”„À⇰‘¥¿¬—πμ√“¬μàÕ À≈Õ¥‡≈Õ◊ ¥º“à π°≈‰°μ“à ßÊ Àπß÷Ë „π°≈‰°¥ß— °≈“à «‰¥·â °°à “√°√–μπÿâ °“√ ß— ‡§√“–Àå fibrinogen ‚¥¬ interleukin (IL)-6 ºà“π∑“ß specific IL-6-sensitive sequence „π fibrinogen gene69 °“√Õ°— ‡ ∫´ßË÷ μ√«®æ∫‰¥®â “°°“√‡æ¡Ë‘ ¢πÈ÷ ¢Õß C-reactive protein (CRP) „π‡≈Õ◊ ¥¢ÕߺªŸâ «É ¬‚√§ ‰μ æ∫‰¥âμ—Èß·μà√–¬–°àÕπ√—∫°“√√—°…“∑¥·∑π‰μ√âÕ¬≈– 30-50 ·≈–æ∫¡“°¢÷Èπ„πºŸâªÉ«¬øÕ°‡≈◊Õ¥·≈– ºªâŸ «É ¬≈“â ߉μ∑“ß™Õà ß∑Õâ ß70-73 ‚¥¬√–¥∫— CRP∑ ’Ë ßŸ ¢π÷È  ¡— æπ— ∏°å ∫— §«“¡‡ ¬’Ë ßμÕà °“√‡°¥‘ ‡Àμ°ÿ “√≥∑å “ßÀ≈Õ¥ ‡≈◊Õ¥À—«„® °“√‡ ’¬™’«‘μ®“°‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥ ·≈–°“√‡ ’¬™’«‘μ®“°∑ÿ° “‡Àμÿ∑’ˇæ‘Ë¡¢÷Èπ 3-5 ‡∑à“ ∑—Èß„π°≈ÿࡪ√–™“°√ª°μ‘ ºŸâªÉ«¬øÕ°‡≈◊Õ¥72-74 ·≈–ºâŸªÉ«¬≈â“߉μ∑“ß™àÕß∑âÕß71, 75-78 Carrero ·≈–§≥– æ∫«à“„π™à«ßªï·√° √–¥—∫ CRP ®–≈¥≈ßÕ¬à“ß¡’π—¬ ”§—≠„πºâŸªÉ«¬øÕ°‡≈◊Õ¥ ·μà‰¡à≈¥≈ß„πºâŸªÉ«¬≈â“ß ‰μ∑“ß™àÕß∑âÕß79 ºâŸ‡¢’¬π —ππ‘…∞“π«à“°“√‰¥â√—∫ heparin ∫àÕ¬Ê ®“°°“√øÕ°‡≈◊Õ¥Õ“®∑”„Àâ°“√Õ—°‡ ∫ ≈¥≈ß  à«π°“√≈â“߉μ∑“ß™àÕß∑âÕßÕ“®‡°‘¥‡¬◊ËÕ∫ÿ™àÕß∑âÕßÕ—°‡ ∫ °“√μ‘¥‡™◊ÈÕ¢Õß “¬ «π™àÕß∑âÕß ¿“«– πÈ”‡°π‘ °“√„™πâ È”¬“∑ª’Ë π‡ªÕóô π endotoxin ·≈–§«“¡‡ªπì bio-incompatibility Õ“®°√–μπÿ⠪ذ‘ √‘ ¬‘ “°“√Õ°— ‡ ∫ ¡°’ “√√°— …“À≈“¬™π¥‘ ∑¡Ë’ º’ ≈≈¥√–¥∫— CRP ≈ß ‡™πà statins80, aspirin81, angiotensin-converting enzyme inhibitors82 À√◊Õ°“√„™âμ—«°√Õß∑’ˇªìπ bio-compatibility ·≈–„™âπÈ” ultrapure „π°“√øÕ°‡≈◊Õ¥83 Õ¬à“߉√°Á¥’¬—߉¡à¡’À≈—°∞“π™—¥‡®π«à“°“√√—°…“‡À≈à“π’È¡’º≈μàÕÕ—μ√“°“√‡ ’¬™’«‘μ¢ÕߺŸâªÉ«¬øÕ°‡≈◊Õ¥ 3.10 Oxidative stress ºâŸªÉ«¬¬√Ÿ ’‡¡’¬®–Õ¬àŸ„π ¿“«– oxidative stress πÕ°®“°π’Ȭ—ß¡’À≈“¬°“√»÷°…“∑’Ëæ∫«à“ “√∑’Ë 152

Practical Guidelines to Reduce Cardiovascular Risk of Dialysis Patients ¡’ƒ∑∏‘Ï antioxidant ™à«¬≈¥§«“¡‡ ’ˬßμàÕ°“√‡°‘¥‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥„πºŸâªÉ«¬øÕ°‡≈◊Õ¥ °“√»÷°…“ the Secondary Prevention with Antioxidants of Cardiovascular disease in End-stage renal disease (SPACE) trial84 ´ß÷Ë »°÷ …“„πºªâŸ «É ¬øÕ°‡≈Õ◊ ¥∑¡’Ë Õ’ “¬ÿ 40-75 ªï ·≈–¡‚’ √§À«— „®·≈–À≈Õ¥‡≈Õ◊ ¥ ®”π«π 196 √“¬ 쥑 μ“¡ ‰ª‡ªìπ√–¬–‡«≈“ 519 «—π æ∫«à“°≈ÿà¡∑’ˉ¥â√—∫ vitamin E ¢π“¥ 800 IU/«—π ¡’§«“¡‡ ’ˬßμàÕ°“√‡°‘¥°≈â“¡ ‡π◊ÈÕÀ—«„®μ“¬≈¥≈ß√âÕ¬≈– 70 ·≈–§«“¡‡ ’ˬßμàÕ°“√‡°‘¥°≈â“¡‡π◊ÈÕÀ—«„®μ“¬ À≈Õ¥‡≈◊Õ¥ ¡ÕßÕÿ¥μ—π ‚√§À≈Õ¥‡≈◊Õ¥ à«πª≈“¬ ·≈– unstable angina ≈¥≈ß√âÕ¬≈– 54 ‡¡◊ËÕ‡∑’¬∫°—∫°≈ÿà¡∑’ˉ¡à‰¥â√—∫ vitamin E Õ’°°“√»÷°…“∑’Ë∑”„πºŸâªÉ«¬øÕ°‡≈◊Õ¥ 134 √“¬ ‚¥¬ ÿà¡„Àâ acetylcysteine ¢π“¥ 600 ¡‘≈≈‘°√—¡ «—π≈– 2 §√—Èß μ‘¥μ“¡‰ª‡ªìπ‡«≈“ 14.5 ‡¥◊Õπ æ∫«à“§«“¡‡ ’ˬßμàÕ°“√‡°‘¥°≈â“¡‡π◊ÈÕÀ—«„®μ“¬∑—Èß∑’ˇ ’¬™’«‘μ·≈– ‰¡à‡ ’¬™’«‘μ °“√‡ ’¬™’«‘μ®“°‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥ °“√∑”©’¥ ’μ√«®À≈Õ¥‡≈◊Õ¥À—«„® À√◊Õ°“√ºà“μ—¥ coronary bypass °“√‡°‘¥À≈Õ¥‡≈◊Õ¥ ¡ÕßÕÿ¥μ—π °“√‡°‘¥‚√§À≈Õ¥‡≈◊Õ¥ à«πª≈“¬∑’ËμâÕßμ—¥Õ«—¬«– À√◊ÕμâÕß´àÕ¡À≈Õ¥‡≈◊Õ¥ ≈¥≈ß√âÕ¬≈– 40 ‡¡◊ËÕ‡∑’¬∫°—∫°≈ÿà¡∑’ˉ¡à‰¥â√—∫ acetylcysteine85 Õ¬à“߉√°Á¥’¬—ß μâÕß°“√°“√»÷°…“„πºŸâªÉ«¬®”π«π¡“°¢÷Èπ °àÕπ®– √ÿª∂÷ß∫∑∫“∑¢Õ߬“„π°≈ÿà¡π’È„π°“√ªÑÕß°—π‚√§ À—«„®·≈–À≈Õ¥‡≈◊Õ¥‰¥â 3.11 Aspirin ªí®®ÿ∫—π¬—߉¡à¡’°“√»÷°…“·∫∫ ÿà¡∑’Ë¡’°“√§«∫§ÿ¡‡°’ˬ«°—∫°“√„™â aspirin ªÑÕß°—π‚√§À—«„® ·≈–À≈Õ¥‡≈◊Õ¥„πºâŸªÉ«¬øÕ°‡≈◊Õ¥ ¡’°“√»÷°…“∑’Ëæ∫«à“°“√„™â aspirin „πºâŸªÉ«¬‚√§‰μ‡√◊ÈÕ√—ߙ૬≈¥°“√ ‡°¥‘ °≈“â ¡‡πÕÈ◊ À«— „®μ“¬ (myocardial infarction) ·μ‰à ¡≈à ¥Õμ— √“‡ ¬’Ë ßμÕà °“√‡ ¬’ ™«’ μ‘ ®“°‚√§À«— „®·≈–À≈Õ¥ ‡≈Õ◊ ¥86´ß÷Ë ª√–‚¬™π∑å ‰’Ë ¥√â ∫— μÕâ ßπ”¡“™ß—Ë °∫— §«“¡‡ ¬’Ë ßμÕà °“√μ°‡≈Õ◊ ¥∑ß—È ‡≈°Á πÕâ ¬·≈–√πÿ ·√ß„π°“√»°÷ …“ the Wave II USRDS Dialysis Morbidity Mortality Study æ∫«à“°“√„™â aspirin „πºâŸªÉ«¬øÕ°‡≈◊Õ¥ 3374 √“¬ ‰¡à‰¥â∑”„Àâ°“√‡°‘¥ acute coronary syndrome ≈¥≈ß ·μà°Á¡’°“√»÷°…“·∫∫ —߇°μ∑’Ëæ∫«à“ aspirin „π ºâŸªÉ«¬‚√§‰μ‡√◊ÈÕ√—ߙ૬≈¥Õ—μ√“°“√‡ ’¬™’«‘μÀ≈—ß®“°‡°‘¥°≈â“¡‡π◊ÈÕÀ—«„®μ“¬‡©’¬∫æ≈—π‰¥8â 7,88 3.12 °“√ Ÿ∫∫Àÿ √’Ë ·¡â®–¡’¢âÕ¡≈Ÿ «à“°“√ Ÿ∫∫ÿÀ√’Ë —¡æ—π∏å°—∫‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥ ‚√§À≈Õ¥‡≈◊Õ¥ ¡Õß ‚√§ À≈Õ¥‡≈Õ◊ ¥·¥ß «à πª≈“¬·≈–°“√‡ ¬’ ™«’ μ‘ ®“°∑°ÿ  “‡Àμ„ÿ πºªŸâ «É ¬øÕ°‡≈Õ◊ ¥89-91 ·μ¬à ß— ‰¡¡à ¢’ Õâ ¡≈Ÿ ®“°°“√ »÷°…“§ÿ≥¿“æ Ÿß«à“ °“√À¬ÿ¥ Ÿ∫∫ÿÀ√’Ë®–¡’ª√–‚¬™πå„π°“√ªÑÕß°—π‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥„πºŸâªÉ«¬ øÕ°‡≈◊Õ¥À√◊Õ‰¡à Õ¬à“߉√°Á¥’‡π◊ËÕß®“°¡’¢âÕ¡Ÿ≈™—¥‡®π∂÷ߧ«“¡ —¡æ—π∏å¢Õß°“√ Ÿ∫∫ÿÀ√’Ë ·π«ªØ‘∫—μ‘μà“ßÊ ∑’Ë¡’„πªí®®ÿ∫—π®÷ß·π–π”„Àâ∫ÿ§§≈“°√ à߇ √‘¡„À⺟âªÉ«¬‡≈‘° ∫Ÿ ∫ÿÀ√’Ë 3.13 °“√ÕÕ°°”≈—ß°“¬ ºâŸªÉ«¬øÕ°‡≈◊Õ¥¡—°¡’§«“¡∑π∑“π„π°“√ÕÕ°°”≈—ß°“¬μË”°«à“°≈ÿࡪ√–™“°√‡æ»·≈–Õ“¬ÿ ‡¥’¬«°—π ¡’¢âÕ¡Ÿ≈«à“§«“¡ “¡“√∂„π°“√ÕÕ°°”≈—ß°“¬«—¥®“° peak oxygen uptake ‡ªìπμ—«∑”𓬰“√ √Õ¥™’«‘μ∑’Ë ”§—≠„πºŸâªÉ«¬øÕ°‡≈◊Õ¥ 175 √“¬ ‡¡◊ËÕμ‘¥μ“¡‰ª‡ªìπ√–¬–‡«≈“‡©≈’ˬ 39 ‡¥◊Õπ92 ·μàªí®®ÿ∫—π ¬—ß‰¡à¡’°“√»÷°…“«à“°“√∑”„À⧫“¡ “¡“√∂„π°“√ÕÕ°°”≈—ß°“¬¥’¢÷Èπ ·≈–/À√◊Õ °“√‡æ‘Ë¡°‘®°√√¡∑“ß 153

Practical Dialysis in the Year 2009 °“¬®–™à«¬≈¥§«“¡‡ ’ˬßμàÕ°“√‡°‘¥‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥·≈–°“√‡ ’¬™’«‘μ„πºŸâªÉ«¬°≈ÿà¡π’È Õ¬à“߉√ °Áμ“¡°“√ÕÕ°°”≈—ß°“¬ “¡“√∂™à«¬§«∫§ÿ¡§«“¡¥—π‚≈À‘μ √–¥—∫‰¢¡—π·≈–πÈ”μ“≈„π‡≈◊Õ¥ ∫ÿ§≈“°√ ®÷ߧ«√ à߇ √‘¡„ÀâºâŸªÉ«¬ÕÕ°°”≈—ß°“¬¡“°¢÷Èπ 3.14 §«“¡Õ«â π ª®í ®∫ÿ π— ¬ß— ‰¡¡à °’ “√»°÷ …“·∫∫¡°’ “√§«∫§¡ÿ ∂ß÷ º≈≈æ— ∏¢å Õß°“√≈¥π”È Àπ°— „πºªâŸ «É ¬øÕ°‡≈Õ◊ ¥ æ∫«à“ºâŸªÉ«¬∑’Ë¡’¥—™π’¡«≈°“¬ (body mass index)  Ÿß —¡æ—π∏å°—∫Õ—μ√“°“√√Õ¥™’«‘μ∑’Ë Ÿß¢÷Èπ ‚¥¬¢÷Èπ°—∫ Õߧåª√–°Õ∫¢Õß√à“ß°“¬¥â«¬ ‚¥¬ª√–‚¬™π凰’ˬ«°—∫°“√√Õ¥™’«‘μ¥—ß°≈à“«æ∫‡©æ“–„π°≈ÿࡺŸâªÉ«¬∑’Ë¡’ ¡«≈°≈â“¡‡π◊ÈÕª°μ‘À√◊ՠߟ ·≈–¡«≈‰¢¡—π„π√à“ß°“¬μË”93  à«π¢âÕ¡≈Ÿ „πºâŸªÉ«¬≈â“߉μ∑“ß™àÕß∑âÕßæ∫«à“¡’ §«“¡À≈“°À≈“¬¡“° ∑ßÈ— ∑æË’ ∫«“à §«“¡Õ«â π ¡— æπ— ∏°å ∫— °“√√Õ¥™«’ μ‘ ∑¥Ë’ ¢’ πÈ÷ 94-96 ‰¡‡à ª≈¬Ë’ π·ª≈ß97, 98 À√Õ◊ ≈¥≈ß99, 100 ¥ß— ππÈ— ®ß÷ ¬ß— ‰¡¡à §’ ”·π–π”„À≈â ¥π”È Àπ°— μ«— ºªŸâ «É ¬·μÀà “°®–∑”μÕâ ß√–¡¥— √–«ß— ‰¡„à À‡â °¥‘ ¿“«– ∑ÿæ‚¿™π“°“√ 3.15 °“√°”®¥— ª®í ®¬— ‡ ¬Ë’ ßμ“à ßÊ ‰ªæ√Õâ ¡°π— ‡πÕË◊ ß®“°ºªâŸ «É ¬øÕ°‡≈Õ◊ ¥¡§’ «“¡´∫— ´Õâ π æ∫‚√§√«à ¡‰¥∫â Õà ¬ ·≈–¡ª’ ®í ®¬— ‡ ¬Ë’ ßμÕà °“√‡°¥‘ ‚√§ À—«„®·≈–À≈Õ¥‡≈◊Õ¥À≈“¬Õ¬à“ß À≈—°°“√√—°…“‡æ◊ËÕ°”®—¥ªí®®—¬‡ ’ˬ߷≈–‚√§√à«¡μà“ßÊ ‰ªæ√âÕ¡°—π ‚¥¬„™â∑’¡∑’˪√–°Õ∫¥â«¬∫ÿ§§≈“°√À≈“¬ª√–‡¿∑πà“®–‡ªìπ«‘∏’∑’Ë¥’„π°“√¥Ÿ·≈ºŸâªÉ«¬ ‡™àπ∑’˪√– ∫º≈  ”‡√Á®„π°“√≈¥§«“¡‡ ’ˬßμàÕ°“√‡°‘¥‡Àμÿ°“√≥å∑“ßÀ—«„®·≈–À≈Õ¥‡≈◊Õ¥„πºâŸªÉ«¬‡∫“À«“π™π‘¥∑’Ë 2 ∑’Ë ¡’ microalbuminuria (the Steno study)101 À√◊Õ°“√≈¥°“√‡ ’¬™’«‘μ„πºâŸªÉ«¬§«“¡¥—π‚≈À‘μ ßŸ ‡æ»™“¬∑’Ë¡’ §«“¡‡ ’ˬߠŸß102 ¡°’ “√»°÷ …“∂ß÷ º≈¢Õß‚ª√·°√¡°“√°”®¥— ª®í ®¬— ‡ ¬’Ë ßÀ≈“¬ª®í ®¬— æ√Õâ ¡°π— „πºªâŸ «É ¬‚√§‰μ√–¬– ∑Ë’ 4 ·≈– 5 ®”π«π 200 √“¬ (LANDMARK - Longitudinal Assessment of Numerous Discrete Modifications of Atherosclerotic Risk Factors in Kidney disease)103 ºªâŸ «É ¬®–∂°Ÿ  ¡àÿ „À‡â ¢“â √∫— °“√√°— …“„π§≈π‘ °‘ ∑¡Ë’ ·’ æ∑¬å ·π–π” ·≈–¡’欓∫“≈§Õ¬°√–μÿâπ‡°’Ë¬«°—∫°“√¥—¥·ª≈ßªí®®—¬‡ ’ˬßμà“ßÊ μàÕ°“√‡°‘¥‚√§À—«„®·≈– À≈Õ¥‡≈Õ◊ ¥Õ¬“à ߇§√ßà §√¥— ‰¥·â °à ‰¢¡π— „π‡≈Õ◊ ¥º¥‘ ª°μ‘ hyperhomocysteinemia §«“¡¥π— ‚≈Àμ‘  ßŸ ‚≈Àμ‘ ®“ß ·≈– øÕ ‡øμ„π‡≈◊Õ¥ ßŸ À√◊Õ∂Ÿ° ÿà¡„À⇢â“√—∫°“√√—°…“μ“¡·π«ªØ‘∫—μ‘∑’Ë„™â„πªí®®ÿ∫—π æ∫«à“ºŸâªÉ«¬°≈ÿà¡ ·√°®–ª√– ∫§«“¡ ”‡√Á®„π°“√§«∫§ÿ¡ªí®®—¬‡ ’ˬßμà“ßÊ ¡“°°«à“ ‰¥â·°à LDL (-30.9 ‡∑’¬∫°—∫ -12.7 ¡‘≈≈‘°√—¡/‡¥´‘≈‘μ√; p=0.001) homocysteine (-0.94 ‡∑’¬∫°—∫ -0.009 ¡‘≈≈‘°√—¡/≈‘μ√; p<0.001) §«“¡¥—π systolic (-6.9 ‡∑’¬∫°—∫ -0.2 ¡‘≈≈‘‡¡μ√ª√Õ∑; p = 0.049) ·≈–§«“¡¥—π diastolic (-4.8 ‡∑’¬∫°—∫ -1.0 ¡‘≈≈‘‡¡μ√ª√Õ∑; p = 0.043) ·μà°≈—∫‰¡àæ∫§«“¡·μ°μà“ß„π carotid intima-media thickness ·≈– brachial artery reactivity ·≈–®”π«π°“√‡ ’¬™’«‘μ®“°‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥ Õ—μ√“°“√‡°‘¥ acute coronary syndrome °“√∑” revascularization ·≈–°“√‡°‘¥‚√§À≈Õ¥‡≈◊Õ¥ ¡Õß∑’ˉ¡à‡ ’¬™’«‘μ°Á‰¡à·μ°μà“ß°—π (23 ‡∑’¬∫°—∫ 19 ‡Àμÿ°“√≥å; p=0.475) ·¡âº≈°“√»÷°…“π’Ȭ—ßμâÕß°“√°“√¬◊π¬—π‚¥¬°“√»÷°…“„πºŸâªÉ«¬ ®”π«π¡“° ·μà°ÁÕ“®æÕ∫Õ°‰¥â«à“°“√¥—¥·ª≈ßªí®®—¬‡ ’ˬßμà“ßÊ ®”‡ªìπμâÕß∑”μ—Èß·μà„π√–¬–·√°Ê ¢Õß‚√§‰μ‡√◊ÈÕ√—ß 154

Practical Guidelines to Reduce Cardiovascular Risk of Dialysis Patients 4.  “‡Àμ∑ÿ °’Ë “√»°÷ …“‡°¬’Ë «°∫— ‚√§À«— „®·≈–À≈Õ¥‡≈Õ◊ ¥„πºªâŸ «É ¬øÕ°‡≈Õ◊ ¥‰¡‰à ¥â º≈ ®–‡ÀÁπ«à“„πªí®®ÿ∫—π¡’°“√»÷°…“·∫∫ ÿà¡·≈–¡’°“√§«∫§ÿ¡‡°’ˬ«°—∫‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥ „πºâŸªÉ«¬øÕ°‡≈◊Õ¥πâÕ¬¡“° °“√»÷°…“∑’Ë¡’Õ¬Ÿà°Á¡’°”≈—߉¡à‡æ’¬ßæÕ„π°“√μ√«®À“§«“¡·μ°μà“ßÕ¬à“ß¡’ π—¬ ”§—≠ ·≈–®”π«πºŸâªÉ«¬∑’ˇ¢â“√à«¡„π°“√»÷°…“°Á§‘¥‡ªìπ —¥ à«ππâÕ¬‡¡◊ËÕ‡∑’¬∫°—∫®”π«πºâŸªÉ«¬øÕ° ‡≈◊Õ¥∑—ÈßÀ¡¥ ®÷ßÕ“®¡’§«“¡≈”‡Õ’¬ß„π°“√‡≈◊Õ°ºŸâªÉ«¬‡¢â“√à«¡°“√»÷°…“  à«π “‡Àμÿ∑’Ë°“√»÷°…“∑’Ë §«∫§ÿ¡ªí®®—¬‡ ’ˬß∑—Ë«‰ª‰¡à‰¥âº≈ Õ“®‡°‘¥®“°°“√„Àâ°“√√—°…“™â“‡°‘π‰ª ∑”„À⇰‘¥°“√‡ª≈’ˬπ·ª≈ß ¢ÕßÀ—«„®·≈–À≈Õ¥‡≈◊Õ¥°àÕπ∑’˺ŸâªÉ«¬‡¢â“√à«¡°“√»÷°…“·≈â« À√◊ÕÕ“®‡°‘¥®“°°“√»÷°…“π—Èπ‰¡à‰¥â¡ÿà߇πâ𠉪∑’Ëªí®®—¬‡ ’ˬß∑’Ë¡’§«“¡ ”§—≠„πºâŸªÉ«¬øÕ°‡≈◊Õ¥ ‡™àπ ‡¡μ–∫Õ≈‘ ¡¢Õß°√–¥°Ÿ ·≈–‡°≈◊Õ·√à À√◊Õ°“√∑’Ë æ∫«à“§«“¡ —¡æ—π∏å√–À«à“ßªí®®—¬‡ ’ˬß∫“ßÕ¬à“ß°—∫‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥„πºŸâªÉ«¬øÕ°‡≈◊Õ¥‡ªìπ„π ∑‘»∑“ßμ√ߢⓡ°—∫ª√–™“°√∑—Ë«‰ª ∑”„À⇰‘¥ ¡¡ÿμ‘∞“π«à“欓∏‘°”‡π‘¥¢Õß‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥„π ºâŸªÉ«¬øÕ°‡≈◊Õ¥·μ°μà“߉ª®“°ª√–™“°√∑—Ë«‰ª °“√√—°…“∑’Ë„™â„π°≈ÿࡪ√–™“°√∑—Ë«‰ª®÷ßÕ“®‰¡à‰¥âº≈„π ºâŸªÉ«¬øÕ°‡≈◊Õ¥ 5. Practical guidelines for prevention cardiovascular disease in dialysis patients ®“°¢âÕ¡≈Ÿ ¢â“ßμâπ æ∫«à“‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥‡ªì𠓇Àμÿ ”§—≠∑’Ë∑”„Àâ‡√“ ≠Ÿ ‡ ’¬ºâŸªÉ«¬ øÕ°‡≈◊Õ¥‰ª °“√ªÑÕß°—π°“√‡°‘¥‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥®÷߇ªìπ‡À¡◊Õπ∫∑ √ÿª ”§—≠∑’Ë®–™à«¬√—°…“ ™’«‘μ¢Õߺ⟪ɫ¬‰«â ·μà„πªí®®ÿ∫—π°≈—∫‰¡à¡’°“√»÷°…“‡°’ˬ«°—∫°“√ªÑÕß°—π‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥„π ºŸâªÉ«¬°≈ÿà¡π’È∑’Ë¡’§ÿ≥¿“æ‡æ’¬ßæÕ ·≈–º≈¢Õß°“√»÷°…“°“√¥—¥·ª≈ßªí®®—¬‡ ’ˬßμàÕ°“√‡°‘¥‚√§À—«„® ·≈–À≈Õ¥‡≈◊Õ¥„πºŸâªÉ«¬°≈ÿà¡π’È°Á‰¡à‰¥âº≈¥—ß∑’˧“¥À«—߉«â¥â«¬‡Àμÿº≈¥—ß°≈à“«¢â“ßμâπ ®÷߇ªìπ°“√¬“°∑’Ë ®–°”Àπ¥·π«ªØ‘∫—쑇æ◊ËÕ°“√ªÑÕß°—π‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥„πºŸâªÉ«¬øÕ°‡≈◊Õ¥ ·μຟ⇢’¬π¡’§«“¡‡ÀÁπ ‡°’ˬ«°—∫°“√ªÑÕß°—π‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥„πºŸâªÉ«¬øÕ°‡≈◊Õ¥¥—ßπ’È 5.1 °“√ªÑÕß°—π°“√‡°‘¥‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥¢ÕߺŸâªÉ«¬‚√§‰μ‡√◊ÈÕ√—ß‚¥¬°”®—¥ªí®®—¬ ‡ ’ˬßμàÕ°“√‡°‘¥‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥ §«√‡√‘Ë¡∑”μ—Èß·μà√–¬–·√°Ê ¢Õß‚√§‰μ‡√◊ÈÕ√—ß ‡π◊ËÕß®“°À“° ª≈àÕ¬„ÀâºâŸªÉ«¬‡¢â“ Ÿà√–¬–∑’ËμâÕß°“√°“√√—°…“∑¥·∑π‰μ ºâŸªÉ«¬°Á¡—°®–‡°‘¥‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥·≈â« ·¡â®–¬—߉¡à· ¥ßÕ“°“√∑“ߧ≈‘π‘°°Áμ“¡ 5.2 „πÀπ«à ¬‰μ‡∑¬’ ¡§«√¡·’ π«∑“ߪØ∫‘ μ— ∑‘ ‰’Ë ¥¡â “μ√∞“π “°≈·≈–¡μ’ “√“ß°“√ªØ∫‘ μ— ™‘ ¥— ‡®π ‡°’ˬ«°—∫¡“μ√∞“π ·≈–°“√¥Ÿ·≈√—°…“√–∫∫‡μ√’¬¡πÈ”∫√‘ ÿ∑∏‘Ï √–∫∫ àßπÈ” ‡§√◊ËÕ߉μ‡∑’¬¡ μ—«°√Õß ‡æ◊ËÕ ∑”„À°â “√øÕ°‡≈Õ◊ ¥¡ª’ √– ∑‘ ∏¿‘ “æ ßŸ ∑ ’Ë ¥ÿ ª√“»®“° “√ªπ‡ªÕóô π∑®’Ë –‡¢“â  ºŸà ªŸâ «É ¬·≈–‰¡‡à °¥‘ ªØ°‘ √‘ ¬‘ “bio- incompatibility „πμ—«ºŸâªÉ«¬ 5.3 ºŸâªÉ«¬μâÕ߉¥â√—∫°“√øÕ°‡≈◊Õ¥Õ¬à“߇撬ßæÕμ“¡¡“μ√∞“π∑’Ë°”À𥂥¬ ¡“§¡‚√§‰μ 155

Practical Dialysis in the Year 2009 ·Ààߪ√–‡∑»‰∑¬ 5.4 ºªŸâ «É ¬§«√¡π’ È”Àπ°— μ«— „°≈‡â §¬’ ß°∫— πÈ”Àπ°— μ«— ·Àßâ ¡“°∑ ’Ë ¥ÿ ·≈–‰¡§à «√¡¿’ “«–·∑√°´Õâ π ®“°°“√øÕ°‡≈◊Õ¥ 5.5 ¡’°“√ª√–‡¡‘π¿“«–‚¿™π“°“√¢ÕߺŸâªÉ«¬‡ªìπ√–¬– ·≈–‡√‘Ë¡„Àâ‚¿™π∫”∫—¥∑—π∑’À“°æ∫ «à“¡’¿“«–∑ÿæ‚¿™π“°“√‡°‘¥¢÷Èπ 5.6 „Àâ°“√√—°…“‡æ◊ËÕ¥—¥·ª≈ßªí®®—¬‡ ’ˬߢÕß‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥μ“¡À—«¢âÕ¢â“ßμâπ ‰¥â·°à 5.6.1 °“√„À⬓°≈ÿà¡ statins ‡æ◊ËÕ≈¥ LDL „ÀâμË”°«à“ 100 ¡‘≈≈‘°√—¡/‡¥´‘≈‘μ√ ·≈– non- HDL cholesterol „ÀâμË”°«à“ 130 ¡‘≈≈‘°√—¡/‡¥´‘≈‘μ√ À√◊Õ„À⬓°≈ÿà¡ fibrate À“°§à“ triglycerides  ßŸ °«à“ 500 ¡‘≈≈‘°√—¡/‡¥´‘≈‘μ√ 5.6.2 °“√§«∫§ÿ¡§«“¡¥—π‚≈À‘μ‚¥¬«‘∏’‰¡à„™â¬“ √à«¡°—∫°“√„™â¬“ ‚¥¬„™â¬“°≈ÿà¡ angiotensin-receptor antagonists À√◊Õ angiotensin-converting enzyme inhibitors ‡ªì𬓰≈ÿà¡·√° §«“¡ ¥—π‚≈À‘μ°àÕπ·≈–À≈—ßøÕ°‡≈◊Õ¥‰¡à§«√ ßŸ °«à“ 140/90 ·≈– 130/80 ¡‘≈≈‘‡¡μ√ª√Õ∑ μ“¡≈”¥—∫ ·≈–‰¡à §«√„Àâ§à“§«“¡¥—π systolic μË”°«à“ 110 ¡‘≈≈‘‡¡μ√ª√Õ∑ 5.6.3 °“√√—°…“ ¡¥ÿ≈øÕ ‡øμ ·§≈‡´’¬¡ ·≈–æ“√“∏—¬√Õ¬¥åŒÕ√å‚¡π„ÀâÕ¬Ÿà„π‡°≥±å∑’Ë °”Àπ¥ 5.6.4 √—°…“¿“«–‚≈À‘μ®“ß‚¥¬„™â erythropoietin ·≈–∏“μÿ‡À≈Á° ‚¥¬√—°…“√–¥—∫ Œ’‚¡‚°≈∫‘π„ÀâÕ¬àŸ√–À«à“ß 11-13 °√—¡/‡¥´‘≈‘μ√ 5.6.5 °“√√—°…“√–¥—∫πÈ”μ“≈„π‡≈◊Õ¥„ÀâÕ¬àŸ„π‡°≥±å 5.6.6 ºªâŸ «É ¬μÕâ ߉¥√â ∫— §”·π–π”„ÀÀâ ¬¥ÿ  ∫Ÿ ∫Àÿ √Ë’ ߥ°“√¥¡Ë◊ ‡§√ÕË◊ ߥ¡Ë◊ ·Õ≈°ÕŒÕ≈å ·≈– ßà ‡ √‘¡„ÀâºâŸªÉ«¬¡’°‘®°√√¡∑“ß°“¬¡“°¢÷Èπ 5.6.7 ºªâŸ «É ¬μÕâ ߉¥√â ∫— §”·π–𔇰¬’Ë «°∫— ‚¿™π∫”∫¥— μß—È ·μ·à √°‡¢“â √∫— °“√øÕ°‡≈Õ◊ ¥·≈– ‰¥â√—∫°“√ª√–‡¡‘π·≈–§”·π–𔇪ìπ√–¬– 5.6.8 °“√√°— …“ hyperhomocysteine ‚¥¬°“√„Àâ folic acid À√Õ◊ «μ‘ “¡π‘ B12 À√Õ◊ «μ‘ “¡π‘ B6 À√Õ◊ acetylcysteine ·¡®â –‰¡¡à ¢’ Õâ ¡≈Ÿ «“à  “¡“√∂≈¥Õμ— √“°“√‡ ¬’ ™«’ μ‘ „πºªâŸ «É ¬‰¥â ·μºà ‡Ÿâ ¢¬’ π°¬Á ß— „Àâ folic acid ¢π“¥ 5-16 ¡‘≈≈‘°√—¡/«—π ·≈–«‘μ“¡‘π∫’√«¡·°àºâŸªÉ«¬ 5.7 °“√√—°…“∑’ËÕ“®¡’∫∑∫“∑„π°“√ªÑÕß°—π°“√‡°‘¥‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥ 5.7.1 Aspirin 5.7.2  “√ Antioxidant ‰¥â·°à «‘μ“¡‘π E ·≈– acetylcysteine 5.7.3  “√μâ“π°“√Õ—°‡ ∫ 6.  √ªÿ  “‡Àμ¢ÿ Õß°“√‡ ¬’ ™«’ μ‘ ¢ÕߺªâŸ «É ¬øÕ°‡≈Õ◊ ¥ª√–¡“≥§√ß÷Ë Àπß÷Ë ‡°¥‘ ®“°‚√§À«— „®·≈–À≈Õ¥‡≈Õ◊ ¥ ´÷Ëß¡’欓∏‘°”‡π‘¥∑’Ë´—∫´âÕπ°«à“„πª√–™“°√∑—Ë«‰ª ªí®®ÿ∫—π¬—ߢ“¥¢âÕ¡Ÿ≈‡°’ˬ«°—∫°“√ªÑÕß°—π‚√§À—«„® 156

Practical Guidelines to Reduce Cardiovascular Risk of Dialysis Patients ·≈–À≈Õ¥‡≈◊Õ¥„πºâŸªÉ«¬°≈ÿà¡π’ÈÕ¬Ÿà¡“° ‚¥¬‡©æ“–¢âÕ¡Ÿ≈∑’Ë¡“®“°°“√»÷°…“·∫∫ ÿà¡·≈–¡’°“√§«∫§ÿ¡ ¢π“¥„À≠à °“√°”Àπ¥·π«ªØ‘∫—쑇æ◊ËÕªÑÕß°—π°“√‡°‘¥‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥„πºŸâªÉ«¬øÕ°‡≈◊Õ¥®÷ß ∑”‰¥â¬“° Õ¬à“߉√°Á¥’°“√√—°…“§ÿ≥¿“æ¢ÕßÀπ૬‰μ‡∑’¬¡„À≥⡓μ√∞“π ∑”°“√øÕ°‡≈◊Õ¥Õ¬à“ß¡’ ª√– ‘∑∏‘¿“æ·≈–‡æ’¬ßæÕ ·≈–°“√¥—¥·ª≈ßªí®®—¬‡ ’ˬßμàÕ‚√§À—«„®·≈–À≈Õ¥‡≈◊Õ¥„πºŸâªÉ«¬‚√§‰μμ—Èß ·μà√–¬–·√°Ê °àÕπ®–¡’°“√‡ª≈’ˬπ·ª≈ß∑’ˉ¡à “¡“√∂ªÑÕß°—π·≈–√—°…“‰¥â √«¡∂÷ß°“√μ‘¥μ“¡¥Ÿ·≈ºŸâ ªÉ«¬Õ¬à“ß„°≈♑¥ °Áπ—∫‡ªìπ∑“߇≈◊Õ°‡¥’¬«„π¢≥–π’È ‡√“§ßμâÕß√Õ¢âÕ¡Ÿ≈‡æ‘Ë¡‡μ‘¡‡æ◊ËÕπ”¡“ª√—∫ª√ÿß·π« ∑’Ë∂◊ժؑ∫—μ‘°—πÕ¬Ÿà √«¡∑—Èß√Õ°“√√—°…“„À¡àÊ ∑’Ë¡’ª√– ‘∑∏‘¿“æ¡“°¢÷Èπ ‡Õ° “√Õ“â ßÕß‘ 1. McDonald S, Excell L. ANZDATA Registry Report 2005. Adelaide, South Australia: Australian and New Zealand Dialysis and Transplant Registry, 2006. 2. United States Renal Data Systems. Annual Data Report. Minneapolis, MN: USRDS, 2006. 3. Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 1998;32:S112-S119. 4. Weiner DE, Tighiouart H, Amin MG, et al. Chronic kidney disease as a risk factor for cardiovascular disease and all- cause mortality: A pooled analysis of community based studies. J Am Soc Nephrol 2004;15:1307-15. 5. Foley RN, Herzog CA, Collins AJ. Smoking and cardiovascular outcomes in dialysis patients: The United States Renal Data System Wave 2 study. Kidney Int 2003;63:1462-7. 6. Keough-Ryan TM, Kiberd BA, Dipchand CS, et al. Outcomes of acute coronary syndrome in a large Canadian cohort: Impact of chronic renal insufficiency, cardiac interventions, and anemia. Am J Kidney Dis 2005;46:845-55. 7. Herzog CA, Ma JZ, Collins AJ. Poor long-term survival after acute myocardial infarction among patients on long-term dialysis. N Engl J Med 1998;339:799-805. 8. Alvestrand A. Carbohydrate and insulin metabolism in renal failure. Kidney Int Suppl 1997; 12:2597-602. 9. Johnson DW, Craven AM, Isbel NM. Modification of cardiovascular risk in hemodialysis patients: An evidence-based review. Hemodialysis Int 2007;11:1-14. 10. Mann JF, Gerstein HC, Pogue J, et al. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: The HOPE randomized trial. Ann Intern Med 2001; 134:629-36. 11. Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342:145- 53. 12. Berl T, Hunsicker LG, Lewis JB, et al. Cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial of patients with type 2 diabetes and overt nephropathy. Ann Intern Med 2003;138:542-9. 13. Garcia-Lopez E, Carrero JJ, Suliman ME, et al. Risk factors for cardiovascular disease in patients undergoing peritoneal dialysis. Perit Dial Int 2007;27(Suppl 2):S205-209. 14. Kalantar-Zadeh K, Block G, Humphreys MH, Kopple JD. Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients. Kidney Int 2003;63:793-808. 15. Coletta AP, Cleland JG, Freemantle N, Clark AL. Clinical trials update from the European Society of Cardiology Heart Failure meeting: SHAPE, BRING-UP 2 VAS, COLA II, FOSIDIAL, BETACAR, CASINO and meta-analysis of cardiac resynchronisation therapy. Eur J Heart Fail 2004;6:673-6. 157

Practical Dialysis in the Year 2009 16. Cice G, Ferrara L, DûAndrea A, et al. Carvedilol increases two-year survival in dialysis patients with dilated cardiomyopathy: A prospective, placebo-controlled trial. J Am Coll Cardiol 2003;41:1438-44. 17. Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: Principal results of the Hypertension Optimal Treatment (HOT) randomized trial. HOT Study Group. Lancet. 1998;351:1755-62. 18. Klahr S, Levey AS, Beck GJ, et al. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group. N Engl J Med.1994;330:877- 84. 19. Foley RN, Parfrey PS, Harnett JD, et al. Impact of hypertension on cardiomyopathy, morbidity and mortality in end- stage renal disease. Kidney Int. 1996;49:1379-85. 20. Wanner C, Krane V, Marz W, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Eng J Med 2005;353:238-48. 21. Tonelli M, Collins D, Robins S, et al. Gemfibrozil for secondary prevention of cardiovascular events in mild to moderate chronic renal insufficiency. Kidney Int 2004;66:1123-30. 22. Uhlig K, Levey AS, Sarnak MJ. Traditional cardiac risk factors in individuals with chronic kidney disease. Semin Dial 2003;16:118-27. 23. Effect of intensive therapy on the development and progression of diabetic nephropathy in the Diabetes Control and Complications Trial. The Diabetes Control and Complications (DCCT) Research Group. Kidney Int 1995;47:1703-20. 24. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837-53. 25. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. N Engl J Med 2000;342:381-9. 26. Alvestrand A. Carbohydrate and insulin metabolism in renal failure. Kidney Int Suppl 1997;62:S48-52. 27. Nishimura M, Murase M, Hashimoto T, et al. Insulin resistance and impaired myocardial fatty acid metabolism in dialysis patients with normal coronary arteries. Kidney Int 2006;69:553-9. 28. Shen Y, Peake PW, Kelly JJ. Should we quantify insulin resistance in patients with renal disease? Nephrology (Carlton) 2005;10:599-605. 29. Besarab A, Bolton WK, Browne JK, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med 1998;339:584-90. 30. Parfrey PS, Foley RN, Wittreich BH, et al. Double-blind comparison of full and partial anemia correction in incident hemodialysis patients without symptomatic heart disease. J Am Soc Nephrol 2005;16:2180-9. 31. Strippoli GF, Craig JC, Manno C, Schena FP. Hemoglobin targets for the anemia of chronic kidney disease: A meta- analysis of randomized, controlled trials. J Am Soc Nephrol 2004;15:3154-3165. 32. Block GA, Hulbert-Shearon TE, Levin NW, Port FK. Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am J Kidney Dis 1998;31:607-17. 33. Noordzij M, Korevaar JC, Bos WJ, et al. Mineral metabolism and cardiovascular morbidity and mortality risk: peritoneal dialysis patients compared with haemodialysis patients. Nephrol Dial Transplant 2006;21:2513.20. 34. Blacher J, Guerin AP, Pannier B, et al. Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension 2001;38:938-42. 158

Practical Guidelines to Reduce Cardiovascular Risk of Dialysis Patients 35. Wang AY, Wang M, Woo J, et al. Cardiac valve calcification as an important predictor for all-cause mortality and cardiovascular mortality in long-term peritoneal dialysis patients: a prospective study. J Am Soc Nephrol 2003;14:159- 68. 36. Amann K, Tornig J, Kugel B, et al. Hyperphosphatemia aggravates cardiac fibrosis and microvascular disease in experimental uremia. Kidney Int 2003;63:1296-301. 37. Haydar AA, Covic a, Colhoun H, et al. Coronary artery calcification and aortic pulse wave velocity in chronic kidney disease patients. Kidney Int 2004;65:1790-4. 38. London GM, Marchais SJ, Guerin AP, et al. Arterial structure and function in end-stage renal disease. Nephrol Dial Transplant 2002;17:1713-24. 39. Wang AY, Woo J, Wang M, et al. Association of inflammation and malnutrition with cardiac valve calcification in continuous ambulatory peritoneal dialysis patients. J Am Soc Nephrol 2001;12:1927-36. 40. Ketteler M, BongartzP, Westenfeld R, et al. Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study. Lancet 2003;361:827-33. 41. Wang AY, Woo J, Lam CW, et al. Association of serum fetuin-A with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients. Nephrol Dial Transplant 2005;20:1676-85. 42. Jung HH, Kim SW, Han H. Inflammation, mineral metabolism and progressive coronary artery calcification in patients on haemodialysis. Nephrol Dial Transplant 2006;21:1915-20. 43. Phan O, Ivanovski O, Nguyen-Khao T, et al. Sevelamer prevents uremia-enhanced atherosclerosis progression in apolipoprotein E-deficient mice. Circulation 2005;112:2875-82. 44. Chertow GM, Burke SK, Raggi P. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 2002;62:245-52. 45. Cunningham J, Danese M, Olson K, et al. Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health-related quality of life in secondary hyperparathyroidism. Kidney Int 2005;68:1793-1800. 46. Pernod G, Bosson JL, Golshayan D, et al. Phenotypic and genotypic risk factors for cardiovascular events in an incident dialysis cohort. Kidney Int 2006;69:1424-30. 47. Kalantar-Zadeh K, Block G, Humphreys MH, Kopple JD. Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients. Kidney Int 2003;63:793-808. 48. Wrone EM, Hornberger JM, Zehnder JL, et al. Randomized trial of folic acid for prevention of cardiovascular events in end-stage renal disease. J Am Soc Nephrol 2004;15:420-6. 49. Suliman ME, Qureshi AR, Barany P, et al. Hyperhomocysteinemia, nutritional status, and cardiovascular disease in hemodialysis patients. Kidney Int 2000;57:1727-35. 50. Balakrishnan VS, Guo D, Rao M, et al. Cytokine gene polymorphism in hemodialysis patients: association with comorbidity, functionality, and serum albumin. Kidney Int 2004;65:1449-60. 51. Losito A, Kalidas K, Santoni S, Jeffery S. Association of interleukin-6-174G/C promoter polymorphism with hypertension and left ventricular hypertrophy in dialysis patients. Kidney Int 2003;64:616-22. 52. Ducloux D, Klein A, Kazory A, et al. Impact of malnutrition-inflammation on the association between homocysteine and mortality. Kidney Int 2006;69:331-5. 53. Scholze A, Rinder C, Beige J, et al. Acetylcysteine reduces plasma homocysteine concentration and improves pulse pressure and endothelial function in patients with end-stage renal failure. Circulation 2004;109:369-74. 54. Bostom AG, Culleton BF. Hyperhomocysteinemia in chronic renal disease. J Am Soc Nephrol 1999;10:891-900. 159

Practical Dialysis in the Year 2009 55. Righetti M, Tommasi A, Lagona C, et al. Effective homocysteine-lowering vitamin B treatment in peritoneal dialysis patients. Perit Dial Int 2004;24:373-7. 56. Owen WF Jr, Lew NL, Liu Y, et al. The urea reduction ratio and serum albumin concentration as predictors of mortality in patients undergoing hemodialysis. N Eng J Med. 1993;329:1001-6. 57. Collins AJ, Ma JZ, Umen A, Keshaviah P. Urea index and other predictors of hemodialysis patient survival. Am J Kidney Dis. 1994;23:272-82. 58. Hakim RM, Breyer J, Ismail N, Schulman G. Effects of dose of dialysis on morbidity and mortality. Am J Kidney Dis. 1994;23:661-9. 59. Lowrie EG, Laird NM, Parker TF, Sargent JA. Effect of the hemodialysis prescription of patient morbidity:Report from the National Cooperative Dialysis Study. N Engl J Med. 1981;305:1176-81. 60. Eknoyan G, Beck GJ, Cheung AK, et al. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med. 2002;347:2010-9. 61. Walsh M, Culleton B, Tonelli M, Manns B. A systematic review of the effect of nocturnal hemodialysis on blood pressure, left ventricular hypertrophy, anemia, mineral metabolism, and health-related quality of life. Kidney Int. 2005;67:1500-8. 62. Charra B, Calemard E, Ruffet M, et al. Survival as an index of adequacy of dialysis. Kidney Int. 1992;41:1286-91. 63. Fagugli RM, Reboldi G, Quintaliani G, et al. Short daily hemodialysis: Blood pressure control and left ventricular mass reduction in hypertensive hemodialysis patients. Am J Kidney Dis. 2001;38:371-6. 64. Kooistra MP, Vos J, Koomans HA, Vos PF. Daily home haemodialysis in The Netherlands: Effects on metabolic control, haemodynamics, and quality of life. Nephrol Dial Transplant. 1998;13:2853-60. 65. Traeger J, Sibai-Galland R, Delawari E, Arkouche W. Daily versus standard hemodialysis: One year experience. Artif Organs. 1998;22:558-63. 66. Jansen MA, Korevaar JC, Dekker FW, et al. Renal function and nutritional status at the start of chronic dialysis treatment. J Am Soc Nephrol 2001;12:157-63. 67. Pifer TB, McCullough KP, Port FK, et al. Mortality risk in hemodialysis patients and changes in nutritional indicators: DOPPS. Kidney Int 2002;62:2238-45. 68. Stenvinkel P, Heimburger O, Paultre F, et al. Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int 1999;55:1899-911. 69. Kaysen GA, Don BR. Factors that affect albumin concentration in dialysis patients and their relationship to vascular disease. Kidney Int 2003;63(Suppl 84):S94-7. 70. Panichi V, Migliori M, De Pietro S, et al. C-reactive protein and interleukin-6 levels are related to renal function in predialytic chronic renal failure. Nephron 2002;91:594-600. 71. Herzig KA, Purdie DM, Brown AM, et al. Is C-reactive protein a useful prognostic marker in peritoneal dialysis patients? J Am Soc Nephrol 2001;12:814-21. 72. Zimmermann J, Herrlinger S, Pruy A, et al. Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int 1999;55:648-58. 73. Yeun JY, Levine RA, Mantadilok V, Kaysen GA. C-Reactive protein predicts all-cause and cardiovascular mortality in hemodialysis patients. Am J Kidney Dis 2000;35:469-76. 74. Iseki K, Tozawa M, Yoshi S, Fukiyama K. Serum C-reactive protein (CRP) and risk of death in chronic dialysis patients. Nephrol Dial Transplant 1999;14:1956-60. 160

Practical Guidelines to Reduce Cardiovascular Risk of Dialysis Patients 75. Noh H, Lee SW, Kang SW, et al. Serum C-reactive protein: A predictor of mortality in continuous ambulatory peritoneal dialysis patients. Perit Dial Int 1998;18:387-94. 76. Haubitz M, Brunkhorst R. C-reactive protein and chronic Chlamydia pneumoniae infection-long-term predictors for cardiovascular disease and survival in patients on peritoneal dialysis. Nephrol Dial Transplant 2001;16:809-15. 77. Wang AY, Woo J, Lam CW, et al. Is a single time point C reactive protein predictive of outcome in peritoneal dialysis patients? J Am Soc Nephrol 2003;14:1871-9. 78. Kim SB, Min WK, Lee SK, et al. Persistent elevation of C-reactive protein and ischemic heart disease in patients with continuous ambulatory peritoneal dialysis. Am J Kidney Dis 2002;39:342-6. 79. Carrero JJ, axilsson J, Avesani CM, et al. Being an inflamed peritoneal dialysis patient-a Danteûs journey. Contrib Nephrol 2006;150:144-51. 80. Chang JW, Yang WS, Min WK, et al. Effects of simvastatin on high-sensitivity C-reactive protein and serum albumin in hemodialysis patients. Am J Kidney Dis 2002;39:1213-7. 81. Ikonomidis I, Andreotti F, Economou E, et al. Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin. Circulation 1999;100:793-8. 82. Stenvinkel P, Andersson P, Wang T, et al. Do ACEinhibitors suppress tumour necrosis factor-alpha production in advanced chronic renal failure? J Intern Med 1999;246:503-507. 83. Stenvinkel P. Inflammation in end-stage renal failure: Could it be treated? Nephrol Dial Transplant. 2002;17(Suppl 8):33-8. 84. Boaz M, Smetana S, Weinstein T, et al. Secondary prevention with antioxidants of cardiovascular disease in end stage renal disease (SPACE): Randomised placebo controlled trial. Lancet 2000;356:1213-8. 85. Tepel M, van der GM, Statz M, et al. The antioxidant acetylcysteine reduces cardiovascular events in patients with end-stage renal failure: A randomized, controlled trial. Circulation 2003;107:992-5. 86. Ruilope LM, Salvetti A, Jamerson K, et al. Renal function and intensive lowering of blood pressure in hypertensive participants of the hypertension optimal treatment (HOT) study. J Am Soc Nephrol. 2001;12:218-25. 87. McCullough PA, Sandberg KR, Borzak S, et al. Benefits of aspirin and beta-blockade after myocardial infarction in patients with chronic kidney disease. Am Heart J. 2002;144:226-32. 88. Berger AK, Duval S, Krumholz HM. Aspirin, beta blocker, and angiotensin-converting enzyme inhibitor therapy in patients with end-stage renal disease and an acute myocardial infarction. J Am Coll Cardiol. 2003;42:201-8. 89. Uhlig K, Levey AS, Sarnak MJ. Traditional cardiac risk factors in individuals with chronic kidney disease. Semin Dial 2003;16:118-27. 90. Cheung AK, Sarnak MJ, Yan G, et al. Atherosclerotic cardiovascular disease risks in chronic hemodialysis patients. Kidney Int 2000;58:353-62. 91. Stack AG, Bloembergen WE. Prevalence and clinical correlates of coronary artery disease among new dialysis patients in the United States: A cross-sectional study. J Am Soc Nephrol 2001;12:1516-23. 92. Sietsema KE, Amato A, Adler SG, Brass EP. Exercise capacity as a predictor of survival among ambulatory patients with end-stage renal disease. Kidney Int 2004;65:719-24. 93. Beddhu S, Pappas LM, Ramkumar N, Samore M. Effects of body size and body composition on survival in hemodialysis patients. J Am Soc Nephrol 2003;14:2366-72. 94. Johnson DW, Herzig KA, Purdie DM, et al. Is obesity a favorable prognostic factor in peritoneal dialysis patients? Perit Dial Int 2000;20:715-21. 161

Practical Dialysis in the Year 2009 95. Fried L, Bernardini J, Piraino B. Neither size nor weight predicts survival in peritoneal dialysis patients. Perit Dial Int 1996;16:357-61. 96. Snyder JJ, Foley RN, Gilbertson DT, et al. Body size and outcomes on peritoneal dialysis in the United States. Kidney Int 2003;64:1838-44. 97. Abbott KC, Glanton CW, Trespalacios FC, et al. Body mass index, dialysis modality, and survival: Analysis of the United States Renal Data System Dialysis Morbidity and Mortality Wave II Study. Kidney Int 2004; 65:597-605. 98. Johansen KL, Young B, Kaysen GA, Chertow GM. Association of body size with outcomes among patients beginning dialysis. Am J Clin Nutr 2004;80:324-32. 99. Stack AG, Murthy BV, Molony DA. Survival differences between peritoneal dialysis and hemodialysis among ùlargeû ESRD patients in the United States. Kidney Int 2004;65:2398-408. 100. McDonald SP, Collins JF, Johnson DW. Obesity is associated with worse peritoneal dialysis outcomes in the Australia and New Zealand patient populations. J Am Soc Nephrol 2003;14:2894-901. 101. Gaede P, Vedel P, Parving HH, Pedersen O. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: The Steno type 2 randomised study. Lancet. 1999; 353:617-22. 102. Agewall S, Fagerberg B, Berglund G, et al. Multiple risk intervention trial in high risk hypertensive men: Comparison of ultrasound intima-media thickness and clinical outcome during 6 years of follow-up. J Intern Med 2001;249:305- 14. 103. Isbel NM, Haluska B, Johnson DW, et al. Increased targeting of cardiovascular risk factors in patients with chronic kidney disease does not improve atheroma burden or cardiovascular function. Am Heart J 2006;151:745-53. 162

Current Management of Anemia in Dialysis Patients 9 Current Management of Anemia in Dialysis Patients æ√‡æ≠Á · ß∂«≈— ¬å 1. ∫∑π” 2.  “‡Àµ¢ÿ Õß¿“«–´¥’ „πºŸâªÉ«¬‰µ«“¬‡√È◊Õ√—ß 3. °“√ª√–‡¡‘π¿“«–´¥’ „πºŸªâ É«¬‰µ«“¬‡√È◊Õ√ß— 4. °“√√—°…“¿“«–´’¥„πºâŸªÉ«¬‰µ«“¬‡√È◊Õ√—ß∑Ë’‰¥√â ∫— °“√√°— …“¥â«¬°“√≈â“߉µ 5. °“√„™â Erythropoietic-stimulating agent (ESA) 6. °“√„™â Adjuvant „πºªâŸ É«¬∑Ë’‰¥â√—∫ ESA 7. Resistant to ESA therapy 8. º≈¢Õß Dialysis µÕà ¿“«–´’¥ 9. °“√√°— …“Õ◊Ëπ„πºŸªâ «É ¬‰µ«“¬‡√ÕÈ◊ √—ß 10.  √ÿª 163

Practical Dialysis in the Year 2009 1. ∫∑π” ‚√§‰µ«“¬‡√◊ÈÕ√—߇ªìπªí≠À“∑’Ë ”§—≠ ·≈–¡’®”π«πºŸâªÉ«¬‡æ‘Ë¡¢÷Èπ∑—Ë«‚≈° „π À√—∞Õ‡¡√‘°“§“¥ °“√≥å«à“ „πªï 2010 ®–¡’ºâŸªÉ«¬∑’˵âÕ߉¥â√—∫°“√√—°…“¥â«¬°“√∫”∫—¥∑¥·∑π‰µ¡“°°«à“ 2 ≈â“π§π ·≈–¡’ §à“„™â®à“¬ Ÿß¡“°„π°“√¥Ÿ·≈1 ¿“«–´’¥‡ªìπªí≠À“·∑√°´âÕπ∑’Ëæ∫∫àÕ¬„πºŸâªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß ¡’§«“¡  —¡æ—π∏å°—∫°“√∑”ß“π¢Õ߉µ∑’Ë≈¥≈ß „πªï 1836 Richard Bright √“¬ß“𧫓¡ —¡æ—π∏å√–À«à“ß¿“«–´’¥ °—∫°“√≈¥≈ߢÕß°“√∑”ß“π¢Õ߉µ ·≈–∂◊Õ«à“¿“«–´’¥‡ªìπ hallmark ¢Õß¿“«– progressive renal failure ·≈–æ∫«à“„πºâŸªÉ«¬øÕ°‡≈◊Õ¥ ¡’§à“ hemoglobin (Hb) ‡©≈’ˬ 7 g/dL ·≈–„πºŸâªÉ«¬∑’ˉ¡à¡’‰µÕ“®¡’§à“ Hb πâÕ¬°«à“ 4 g/dL 2 §«“¡™°ÿ ¢Õß¿“«–´¥’ „πºªâŸ «É ¬‰µ«“¬‡√Õ◊È √ß— ·µ°µ“à ß°π— „π·µ≈à –√“¬ß“π¢π÷È °∫— ª∑ï »’Ë °÷ …“°≈¡ÿà ª√–™“°√∑’Ë·µ°µà“ß°—π„π·ßà‡™◊ÈÕ™“µ‘ ‚√§∑’ˇªì𠓇Àµÿ¢Õß‚√§‰µÀ√◊Õ‚√§√à«¡ √«¡‰ª∂÷߬—ß¡’§«“¡·µ° µà“ߢÕß√–¥—∫°“√∑”ß“π¢Õ߉µ∑’ˇ√‘Ë¡æ∫¿“«–´’¥ ®“°°“√»÷°…“ Prevalence of Anemia in Early Renal Insufficiency (PAERI) Study ∑”°“√  ”√«®„π À√—∞ „π™à«ß °.§. 2000 - ∏.§. 2001 »÷°…“ºŸâªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß 5,222 √“¬ ºâŸªÉ«¬À≠‘ß¡’§à“ serum creatinine √–À«à“ß 1.5-6 mg/dL ·≈–ºŸâªÉ«¬™“¬∑’Ë¡’§à“ serum creatinine √–À«à“ß 2-6 mg/dL æ∫«à“ √âÕ¬≈– 47.7 ¡’§à“ Hb µË”°«à“À√◊Õ‡∑à“°—∫ 12 g/dL √âÕ¬≈– 7.3 ¢ÕߺŸâªÉ«¬™“¬ ·≈–√âÕ¬≈– 10.3 ¢ÕߺŸâªÉ«¬ À≠‘ß¡’§à“ Hb µË”°«à“À√◊Õ‡∑à“°—∫ 10 g/dL §«“¡™ÿ°¢Õß¿“«–´’¥·¬°µ“¡‚√§æ∫«à“√âÕ¬≈– 53.8 ¢Õß ºŸâªÉ«¬‡∫“À«“π¡’¿“«–´’¥  à«πºŸâªÉ«¬ vascular disease æ∫¿“«–´’¥√âÕ¬≈– 43.6 ·≈–§«“¡™ÿ°¢Õß¿“«– ´’¥æ∫¡“°¢÷Èπ‡¡◊ËÕ°“√∑”ß“π¢Õ߉µ≈¥≈ß ‚¥¬∂â“ GFR ¡“°°«à“À√◊Õ‡∑à“°—∫ 60 ml/min/1.73m2 æ∫«“à √Õâ ¬ ≈– 26.7 ¡’ Hb πâÕ¬°«à“À√◊Õ‡∑à“°—∫ 12 g/dL ·µàæ∫¡“°¢÷Èπ‡ªìπ√âÕ¬≈– 75.5 3 „π°≈ÿà¡∑’Ë GFR πâÕ¬°«à“ 15 ml/min/ 1.73m2 ®“°¢âÕ¡Ÿ≈¢Õß NHANES III »÷°…“ºâŸªÉ«¬ 15,971 √“¬ „π™à«ßªï 1988-1994 æ∫«à“ Hb ‡√‘Ë¡≈¥ ≈߇¡◊ËÕ creatinine clearance πâÕ¬°«à“À√◊Õ‡∑à“°—∫ 70 ml/min „πºŸâ™“¬ ·≈–πâÕ¬°«à“À√◊Õ‡∑à“°—∫ 50 ml/min „πºÀ⟠≠ß‘ ‚¥¬º™âŸ “¬¡‚’ Õ°“ ∑®’Ë –æ∫¿“«–´¥’ ‰¥∫â Õà ¬°«“à ºÀ⟠≠ß‘ ∑√’Ë –¥∫— °“√∑”ß“π¢Õ߉µ‡¥¬’ «°π— 4 ·µ®à “° NHANES IV æ∫«à“§«“¡™ÿ°≈¥≈ß Õ“®‡ªìπº≈®“°«‘∏’°“√»÷°…“·≈–°“√‡ª≈’ˬπ·ª≈ß·π«∑“ß°“√√—°…“ „πºªâŸ «É ¬‡∫“À«“πÕ“®‡ ¬Ë’ ßµÕà ¿“«–´¥’ ·≈–¡°’ “√≈¥≈ߢÕß Hb ‰¥‡â √«Á °«“à ºªŸâ «É ¬∑‰Ë’ ¡‡à ªπì ‡∫“ À«“π ®“°°“√»÷°…“¢Õß New JP ·≈–§≥– æ∫«à“„πºâŸªÉ«¬‡∫“À«“π¡’°“√≈¥≈ߢÕß Hb ‡¡◊ËÕ eGFR πâÕ¬°«à“ 83 ml/min5 ®“° USRDS 2007 „πªï 2006 Hb ‡©≈’ˬ¢≥–∑’ˇ√‘Ë¡≈â“߉µ „πºŸâªÉ«¬øÕ°‡≈◊Õ¥‡∑à“°—∫ 10.2 g/ dL ·≈– 10.8 g/dL  ”À√—∫ºâŸªÉ«¬≈â“߉µ∑“ß™àÕß∑âÕß ®–‡ÀÁπ‰¥â«à“¿“«–´’¥æ∫‰¥â∫àÕ¬„πºâŸªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß ·≈–‡√‘Ë¡¡’°“√≈¥≈ߢÕß Hb µ—Èß·µà°“√ ∑”ß“π¢Õ߉µ≈¥≈߉¡¡à “° ¥ß— ππ—È °“√µ¥‘ µ“¡ Hb ®ß÷ ¡§’ «“¡ ”§≠— „πºªŸâ «É ¬‰µ«“¬‡√Õ◊È √ß— DOQI ‰¥·â π–π” „Àâ«—¥§à“ Hb „πºŸâªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß∑ÿ°√“¬ ‚¥¬‰¡à¢÷Èπ°—∫√–¬–¢Õß‚√§·≈– “‡Àµÿ¢Õß‚√§‰µ ‚¥¬§«√µ√«® Õ¬à“ßπâÕ¬∑ÿ°ªï ‡°≥±å°“√«‘π‘®©—¬¿“«–´’¥ §◊Õ Hb πâÕ¬°«à“ 13.5 g/dL „πºâŸ™“¬, πâÕ¬°«à“ 12 g/dL „πºŸâ À≠‘ß  ”À√—∫ WHO „™â‡°≥±å Hb πâÕ¬°«à“ 13 g/dL „πºŸâ™“¬ ·≈–πâÕ¬°«à“ 12 g/dL „πºŸâÀ≠‘ß °“√§âπÀ“ 164

Current Management of Anemia in Dialysis Patients ºŸâªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß∑’Ë¡’¿“«–´’¥µ—Èß·µà·√°®–∑”„Àâ “¡“√∂„Àâ°“√¥Ÿ·≈·≈–Õ“®ªÑÕß°—π¿“«–·∑√°´âÕπ∑’Ë ®–‡°‘¥®“°¿“«–´’¥‰¥â ‡™àπ °“√‡¢â“√—∫°“√√—°…“„π‚√ß欓∫“≈, cardiovascular disease, cognitive impairment ·≈–°“√‡ ’¬™’«‘µ 6,7 2.  “‡Àµ¢ÿ Õß¿“«–´’¥„πºªŸâ «É ¬‰µ«“¬‡√◊ÈÕ√ß—  “‡Àµÿ¢Õß¿“«–´’¥„πºâŸªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß8,9 1. erythropoiesis ≈¥≈ß ®“°°“√ √â“ß erythropoietin ≈¥≈ß∑’ˉµ 2. resistant ¢Õ߉¢°√–¥Ÿ°µàÕ erythropoietin 3. red blood cell survival  —Èπ≈ß 4. °“√¬—∫¬—Èß erythropoiesis ‚¥¬ toxic metabolites 5. °“√ ≠Ÿ ‡ ’¬‡≈◊Õ¥ °“√¢“¥ erythropoietin ‡ªìπ°≈‰° ”§—≠¢Õß°“√‡°‘¥¿“«–´’¥„πºŸâªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß ‚¥¬√âÕ¬ ≈– 90  √â“ß∑’ˉµ ·≈–√âÕ¬≈– 10  √â“ß∑’˵—∫ Àπâ“∑’Ë¢Õß erythropoietin §◊Õ°√–µÿâπ terminal differentiation ¢Õß erythroid progenitor „π‰¢°√–¥°Ÿ , ‡æ‘Ë¡°“√ √â“ß Hb, ∑”„Àâ reticulocyte „π‰¢°√–¥Ÿ°ÕÕ°‰ª àŸ°√–·  ‡≈◊Õ¥°àÕπ°”À𥇫≈“ ®“°°“√»°÷ …“«¥— √–¥∫— erythropoietin „π‡≈Õ◊ ¥¢ÕߺªŸâ «É ¬‰µ«“¬‡√ÕÈ◊ √ß— æ∫«“à Õ¬„àŸ π‡°≥±ªå °µ‘  ”À√—∫§π∑’Ë¡’§à“ Hct Õ¬Ÿà„π√–¥—∫ª°µ‘ §◊Õ 13-21 mU/ml ·µà„π§π∑’ˉµ∑”ß“πª°µ‘·≈–´’¥ ®–¡’√–¥—∫¢Õß erythropoietin „π‡≈◊Õ¥ Ÿß¢÷Èπ‡ªìπ 10-100 ‡∑à“¢Õß§à“ª°µ‘ ·≈–·¡â·µà„πºâŸªÉ«¬∑’ˉ¡à¡’‰µ°Á¬—ß “¡“√∂µ√«® æ∫√–¥—∫ erythropoietin ‰¥â · ¥ß«à“¿“«–°“√¢“¥ erythropoietin „πºâŸªÉ«¬‰µ«“¬‡√◊ÈÕ√—ßπà“®–‡ªìπ relative deficiency ®“°°“√»÷°…“‚¥¬„™â radioisotope study æ∫«à“‡¡Á¥‡≈◊Õ¥·¥ß¢ÕߺŸâªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß ¡’ mild hemolysis ∑”„Àâ red cell survival  —Èπ°«à“ª°µ‘ ·µà¬—߉¡à√Ÿâ “‡Àµÿ·πàπÕπ9 „πªï 1966 ¡’°“√»÷°…“æ∫ uremic toxin ´÷Ë߇™◊ËÕ«à“¡’º≈¬—∫¬—Èß°“√ √â“߇¡Á¥‡≈◊Õ¥·¥ß ‚¥¬‡¡◊ËÕ π” uremic serum ¡“ incubate °—∫ murine marrow cell „π¿“«–∑’Ë¡’ growth factor, erythropoietin æ∫«à“ in vitro erythropoiesis ‡ ¬’ ‰ª ®“°°“√»°÷ …“„π uremic nephrectomized rabbit æ∫«“à potential erythropoietic toxin ‰¥â·°à polyamines ‡™àπ spermine, spermidine, putrescine, cadaverine, parathyroid hormone ´÷Ëß “√ ‡À≈à“π’ȇªìπ bone marrow toxin ·µà‰¡à‡®“–®ß°—∫‡¡Á¥‡≈◊Õ¥·¥ß πÕ°®“°π’Ȭ—ß¡’°“√§âπæ∫ polymeric polyamine-protein conjugate ∑’Ë¡’º≈µàÕ CFU-E ·µà‰¡à¡’º≈µàÕ BFU-E  “√Õ◊Ëπ∑’Ë¡’º≈µàÕ°“√ √â“߇¡Á¥‡≈◊Õ¥·¥ß ‡™àπ quinolinic acid ‡ªìπ product ®“°°“√ oxidation ¢Õß tryptophan  “√π’È – ¡„π¿“«–‰µ«“¬ ¡’º≈∑”„À⇰‘¥ apoptosis ¢Õ߇´≈≈å º≈°“√»÷°…“ in vivo ·≈– in vitro æ∫«à“ “√π’È¡’º≈¬—∫¬—Èß hypoxia ·≈– cobalt-induced epo gene expression 8,10 πÕ°®“° uremic toxin ·≈â« ¬—ß¡’ inflammatory cytokine ´÷Ëß¡’º≈µàÕ°“√ √â“߇¡Á¥‡≈◊Õ¥·¥ß „πºŸâªÉ«¬øÕ°‡≈◊Õ¥ ¡’√–¥—∫ IL-6 ‡æ‘Ë¡¢÷Èπ 8-10 ‡∑à“ ·≈–√–¥—∫¢Õß IL-6 ¡’§«“¡ —¡æ—π∏å°—∫ poor outcome, 165

Practical Dialysis in the Year 2009 ¢π“¥¢Õß erythropoietin ∑’Ë„™â„π°“√·°â‰¢¿“«–´’¥ æ∫«à“ IL-6 ¡’º≈µâ“πƒ∑∏‘Ï¢Õß erythropoietin µàÕ bone marrow proliferation8 æ∫«“à „πºªâŸ «É ¬øÕ°‡≈Õ◊ ¥√Õâ ¬≈– 35-65 ¡√’ –¥∫— C-reactive protein (CRP) „π‡≈Õ◊ ¥ ßŸ °«“à ª°µ‘ ´÷Ëß∫àß∂÷ß¿“«–Õ—°‡ ∫ §‘¥«à“‡°‘¥®“° impaired clearance of cytokines, ¡’°“√ – ¡¢Õß advanced glycation end product, unrecognized infection ´÷Ëß°“√Õ—°‡ ∫π’È¡’º≈°¥°“√ √â“߇¡Á¥‡≈◊Õ¥·¥ß ®“°°“√»÷°…“¢Õß Barany ·≈–§≥– æ∫«à“ºâŸªÉ«¬øÕ°‡≈◊Õ¥∑’Ë¡’√–¥—∫ CRP ¡“°°«à“À√◊Õ‡∑à“°—∫ 20 mg/L ®–µâÕß„™â¢π“¥ ¢Õß erythropoietic stimulating agent (ESA) ¡“°°«à“°≈ÿà¡∑’Ë√–¥—∫ CRP µË”°«à“∂÷ß√âÕ¬≈– 80 ·≈–°“√ »°÷ …“‚¥¬ Gunnell ·≈–§≥– „πºªŸâ «É ¬øÕ°‡≈Õ◊ ¥·≈–≈“â ߉µ∑“ß™Õà ß∑Õâ ß °æÁ ∫§«“¡ ¡— æπ— ∏√å –À«“à ß√–¥∫— CRP °—∫ epo/Hct ratio, r = 0.337, p=0.0018 „πºªŸâ «É ¬‰µ«“¬‡√ÕÈ◊ √ß— ¡§’ «“¡º¥‘ ª°µ¢‘ Õß°“√∑”ß“π¢Õ߇°√¥Á ‡≈Õ◊ ¥ ®“°°“√∑¡Ë’ ’ platelet factor 3 activity ≈¥≈ß, PGI2 ‡æ‘Ë¡¢÷Èπ, thromboxane A2 ≈¥≈ß ·≈– suboptimal FVIII:vWF complex activity ´÷Ëß °“√∑”ß“π¢Õ߇°√¥Á ‡≈Õ◊ ¥∑ºË’ ¥‘ ª°µπ‘ ÕÈ’ “®∑”„À¡â ’ occult GI bleeding À√Õ◊ ‡≈Õ◊ ¥ÕÕ°®“°µ”·Àπßà ÕπË◊ ∑”„Àâ ‡°‘¥¿“«–´’¥9 3. °“√ª√–‡¡π‘ ¿“«–´’¥„πºŸªâ «É ¬‰µ«“¬‡√ÕÈ◊ √ß— DOQI ·π–π”„Àâµ√«® CBC ‡æ◊ËÕª√–‡¡‘π¿“«–´’¥„πºŸâªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß ´÷Ëß®– “¡“√∂∫Õ° §«“¡√πÿ ·√ß·≈– “‡Àµ¢ÿ Õß¿“«–´¥’ ‰¥â °“√ª√–‡¡π‘ Hb ¥°’ «“à Hct ‡æ√“–§“à Hb stable °«“à ·≈– “¡“√∂ «¥— ‰¥‚â ¥¬µ√ß “¡“√∂‡°∫Á µ«— Õ¬“à ߇≈Õ◊ ¥‰«‚â ¥¬‰¡¡à º’ ≈µÕà §“à Hb ·≈–°“√·°«ßà ¢Õߧ“à µË”°«“à Hct ®ß÷ ·π–π” „Àâ„™â Hb ‡ªìπ«‘∏’¡“µ√∞“π„π°“√ª√–‡¡‘π¿“«–´’¥11 ‡π◊ËÕß®“°„πºâŸªÉ«¬øÕ°‡≈◊Õ¥ Hb ¡’°“√‡ª≈’ˬπ·ª≈ß µ“¡ interdialytic fluid weight gain ·≈– ultrafiltration ®÷ߧ«√«—¥∑’Ë midweek predialysis ·µà‡π◊ËÕß®“°¬—ß ‰¡à¡’¢âÕ¡Ÿ≈«à“«—𠇫≈“∑’Ë«—¥¡’º≈µàÕ outcome ¥—ßπ—Èπ°“√«—¥ Hb  “¡“√∂∑”°àÕπøÕ°‡≈◊Õ¥«—π„¥°Á‰¥â °“√µ√«® CBC ¬—ß “¡“√∂¥§Ÿ à“ MCV ´÷Ëß∂â“ Ÿß §‘¥∂÷ß megaloblastic anemia ®“°°“√¢“¥ «‘µ“¡‘π B12, folate ∂â“ MCV µË” Õ“®‡°‘¥®“° iron deficiency anemia, thalassemia ·≈–°“√¥≈Ÿ —°…≥– hypochromic red blood cell ∫àß∂÷ß¿“«–°“√¢“¥‡À≈Á° ≈°— …≥–¢Õ߇¡¥Á ‡≈Õ◊ ¥·¥ß„πºªŸâ «É ¬‰µ«“¬‡√Õ◊È √ß— ‡ªπì normochromic normocytic ‡À¡Õ◊ π anemia of chronic disease πÕ°®“°π¬È’ ß—  “¡“√∂µ√«® reticulocyte index, absolute reticulocyte count, reticulocyte production index ‡æ◊ËÕ∫Õ°∂÷ß proliferative activity ¢Õ߉¢°√–¥°Ÿ ´÷Ëß®–¡’§à“µË”„πºâŸªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß CBC ¬ß— „À¢â Õâ ¡≈Ÿ ∑Õ’Ë “®∫ßà ∂ß÷ §«“¡º¥‘ ª°µ¢‘ Õ߉¢°√–¥°Ÿ ‡™πà ¡–‡√ßÁ ‡¡¥Á ‡≈Õ◊ ¥multiple myeloma ‚¥¬Õ“®· ¥ß„Àâ‡ÀÁπ∂÷ߧ«“¡º‘¥ª°µ‘¢Õ߇¡Á¥‡≈◊Õ¥¢“« ‡°√Á¥‡≈◊Õ¥ ´÷Ë߇ªìπ¢âÕ∫àß™’È„π°“√µ√«®æ‘‡»…‡æ‘Ë¡ ‡µ‘¡ √«¡∂÷ß°“√µ√«®‰¢°√–¥Ÿ°‡æ◊ËÕ¬◊π¬—π°“√«‘π‘®©—¬µàÕ‰ª ®“° European Best Practice Guideline (EBPG) ‰¥â·π–π”„Àâ àßµ√«®æ‘‡»…‡æ‘Ë¡‡µ‘¡‡¡◊ËÕ¡’¢âÕ ∫ßà ™‡’È æÕ◊Ë À“ “‡Àµ¢ÿ Õß¿“«–´¥’ ‰¥·â °à °“√À“ occult GI blood loss, serum B12, red cell folate concentration, parathyroid hormone, test for hemolysis (haptoglobin, LDH, bilirubin, coombsû test), plasma/serum, urine protein electrophoresis/immunoblotting, serum aluminium, Hb electrophoresis 166

Current Management of Anemia in Dialysis Patients °“√„Àâ°“√«‘π‘®©—¬¿“«–´’¥µ“¡ EBPG π—Èπ ºŸâªÉ«¬§«√¡’°“√∑”ß“π¢Õ߉µ≈¥≈ß„π√–¥—∫∑’Ë ∑”„À⇰‘¥Õ“°“√´’¥‰¥â ·≈–‰¡à¡’ “‡ÀµÿÕ◊Ëπ∑’Ë®–Õ∏‘∫“¬ ‚¥¬®“° NHANES III æ∫«à“¡’‡æ’¬ß√âÕ¬≈–1 ¢Õß °≈ÿà¡∑’Ë GFR ¡“°°«à“ 60 ml/min ∑’Ë¡’ Hb πâÕ¬°«à“ 12 g/dL „πºâŸ™“¬ ·≈– πâÕ¬°«à“ 11 „πºŸâÀ≠‘ß ·µà°Á¡’ √“¬ß“π∑’Ë√âÕ¬≈– 25 ¢Õߺ⟪ɫ¬‰µ«“¬‡√◊ÈÕ√—ß∑’Ë GFR ¡“°°«à“ 50 ml/min ∑’Ë¡’ Hb πâÕ¬°«à“ 12 g/dL12 °“√µ√«®√–¥∫— erythropoietin „π‡≈Õ◊ ¥‡æÕË◊ °“√«π‘ ®‘ ©¬— ¿“«–´¥’ „πºªŸâ «É ¬‰µ«“¬‡√ÕÈ◊ √ß— ππÈ— ‰¡‰à ¥â ·π–π”„Àâµ√«®„π DOQI ·µà EBPG ·π–π”«à“ Õ“®æ‘®“√≥“µ√«®√–¥—∫ erythropoietin ∂â“æ∫¿“«–´’¥ „πºâŸªÉ«¬∑’Ë√–¥—∫°“√∑”ß“π¢Õ߉µ¬—߉¡à≈¥≈ß¡“° GFR 60-120 ml/min12 4. °“√√°— …“¿“«–´¥’ „πºâªŸ É«¬‰µ«“¬‡√Õ◊È √ß— ∑’‰Ë ¥√â ∫— °“√√°— …“¥â«¬°“√≈â“߉µ ºŸâªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß¡’§ÿ≥¿“æ™’«‘µ∑’Ë≈¥≈ß ¡’§«“¡‡ ’ˬߵàÕ cardiovascular disease ¡’Õ—µ√“°“√ ‡ ’¬™’«‘µ ßŸ °«à“ª√–™“°√∑—Ë«‰ª ¡’√“¬ß“π„π moderate to severe chronic kidney disease √âÕ¬≈– 40 ¡’ heart failure ‡æ‘Ë¡‡ªìπ√âÕ¬≈– 75 ‡¡◊ËÕ‡¢â“ Ÿà‰µ«“¬√–¬– ÿ¥∑⓬13 ¿“«–´’¥‡ªìπªí≠À“·∑√°´âÕπ∑’Ëæ∫‰¥â ∫àÕ¬„πºŸâªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß ·≈–æ∫«à“§«“¡√ÿπ·√ߢÕß¿“«–´’¥‡ªìπµ—«∑”𓬰“√≈¥≈ߢÕß survival „π ºâŸªÉ«¬∑’ˇ√‘Ë¡≈â“߉µ14 Physiological adaptation ¢Õß√“à ß°“¬µÕà ¿“«–´¥’ ¡’ cardiac output ¡“°¢πÈ÷ , ¡°’ “√‡æ¡Ë‘ oxygen affinity ¢Õß Hb, ‡æ¡‘Ë cardiac work ‡æÕ◊Ë √°— …“√–¥∫— ÕÕ°´‡‘ ®π∑‰’Ë ª‡≈¬’È ß‡πÕ◊È ‡¬Õ◊Ë µ“à ßÊ ∑”„À‡â °¥‘ left ventricular hypertrophy µ“¡¡“2 ¿“«–´’¥‡ªìπªí®®—¬‡ ’ˬߢÕß°“√‡°‘¥ left ventricular hypertrophy, heart failure ∑”„Àâ‡æ‘Ë¡ cardiovascular morbidity, mortality ·≈–¬—ß¡’º≈µàÕ cognitive function ·≈–§ÿ≥¿“æ™’«‘µ °“√√—°…“¿“«– ´’¥ ™à«¬ª√—∫ª√ÿߧÿ≥¿“æ™’«‘µ, exercise tolerance, sexual function, glucose metabolism, clotting function ·≈–≈¥ total health care cost ‰¥â‚¥¬¡√’ “¬ß“π “¡“√∂≈¥§à“„™â®à“¬‰¥â 411 ¥Õ≈≈“√ å À√—∞µÕà §πµÕà ‡¥◊Õπ ‚¥¬≈¥§“à „™®â “à ¬„π¢≥–‡¢“â √∫— °“√√°— …“„π‚√ß欓∫“≈·≈–§“à √°— …“欓∫“≈©°ÿ ‡©π‘ 15 ®“° meta-analysis æ∫«à“„πºŸâªÉ«¬ dialysis °“√‰¥â√—∫ erythropoietin ∑”„Àâ Hb ‡æ‘Ë¡¢÷Èπ®“°πâÕ¬°«à“ 8 ‡ªìπ¡“°°«à“ 11 g/dL ·≈–¡§’ ≥ÿ ¿“晫’ µ‘ ¥¢’ π÷È √Õâ ¬≈–10-70 “¡“√∂Õµ— √“°“√‡¢“â √∫— °“√√°— …“„π‚√ß欓∫“≈·≈–°“√‰¥√â ∫— ‡≈Õ◊ ¥ ‰¥â16 ¢âÕ¡≈Ÿ ®“° DOPPS æ∫«à“ case-mix-adjusted mortality and hospitalization risk ≈¥≈ß√âÕ¬≈– 5 ·≈– 6 µÕà Hb 1 g/dL ∑‡Ë’ æ¡Ë‘ ¢πÈ÷ ®“° baseline µ“¡≈”¥∫— (p≤0.003) ·≈– patient mortality and hospitalization risk ≈¥≈ß√âÕ¬≈– 10-12 ∑ÿ° Hb 1 g/dL ∑’ˇæ‘Ë¡¢÷Èπ¡“°°«à“ mean Hb17 ¢âÕ¡≈Ÿ ®“°°“√»÷°…“¢Õß Levin A ·≈–§≥– æ∫«à“¿“«–´’¥°àÕπ‡√‘Ë¡ dialysis ¡’§«“¡ —¡æ—π∏å °∫— Õµ— √“µ“¬∑ ’Ë ßŸ ¢π÷È ®“°¢Õâ ¡≈Ÿ °“√»°÷ …“„πºªâŸ «É ¬ 15,807 √“¬ æ∫«“à °“√„Àâ erythropoietin °Õà π‡√¡‘Ë dialysis  —¡æ—π∏å°—∫°“√≈¥≈ߢÕߧ«“¡‡ ’ˬ߄π°“√‡ ’¬™’«‘µ ‡¡◊ËÕ‡∑’¬∫°—∫°“√‡√‘Ë¡À≈—ß dialysis ‚¥¬¡’ adjusted risk ratio 0.87 (95% CI 0.82-0.92)1 ·≈–√“¬ß“π‚¥¬ Wish JB ·≈–§≥–„πºâŸªÉ«¬øÕ°‡≈◊Õ¥ 5,848 √“¬ æ∫«à“ ºŸâªÉ«¬∑’ˉ¥â√—∫ erythropoietin °àÕπ dialysis ¡’√âÕ¬≈– 52 ·≈–¡’ risk for cardiovascular event µË”°«à“ RR 0.7 (95%CI 0.61-0.82) ·≈– RR for acute myocardial infarction 0.65 (95% CI 0.44-0.95), RR for death 0.52 (95%CI 0.4-0.68)18 167

Practical Dialysis in the Year 2009 ®“°¢Õâ ¡≈Ÿ ®–‡ÀπÁ ‰¥«â “à ¿“«–´¥’ ¡º’ ≈µÕà °“√欓°√≥‚å √§„πºªŸâ «É ¬‰µ«“¬µß—È ·µ°à Õà π‡√¡‘Ë dialysis ·≈– àߺ≈µàÕ°“√欓°√≥å‚√§À≈—ß®“°‡√‘Ë¡ dialysis ¥â«¬ ¥—ßπ—Èπ°“√„Àâ°“√¥Ÿ·≈ºŸâªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß„π°“√ ·°‰â ¢¿“«–´¥’ µß—È ·µ‡à √¡‘Ë ·√°¡§’ «“¡ ”§≠— ·≈–√–¥∫— §«“¡√πÿ ·√ߢÕß¿“«–´¥’ °‡Á ªπì ª®í ®¬— ∑¡’Ë §’ «“¡ ”§≠— °“√·°â‰¢¿“«–´’¥πà“®–™à«¬∑”„Àâ°“√欓°√≥å‚√§·≈–Õ—µ√“°“√√Õ¥™’«‘µ¢Õߺ⟪ɫ¬‰µ«“¬‡√◊ÈÕ√—ߥ’¢÷Èπ ®“°°“√»÷°…“‚¥¬ Drueke TB ·≈–§≥– „π CREATE study (Cardiovascular risk reduction by early anemia treatment with epoetin-beta) ‡ª√’¬∫‡∑’¬∫√–¥—∫ Hb 13-15 g/dL °—∫ 10.5-11.5 „πºŸâªÉ«¬ predialysis µ‘¥µ“¡ 3 ªï æ∫«à“‰¡à¡’§«“¡·µ°µà“ß„π first cardiovascular event ·≈– left ventricular mass index ·µà„π°≈ÿà¡∑’Ë¡’ Hb  Ÿß°«à“¡’§ÿ≥¿“æ™’«‘µ¥’°«à“19 ®“° CHOIR trial »°÷ …“„πºªŸâ «É ¬‰µ«“¬‡√ÕÈ◊ √ß— ∑¬Ë’ ß— ‰¡‰à ¥‡â √¡Ë‘ dialysis „Àâ epoetin-α ‡ª√¬’ ∫‡∑¬’ ∫ Hb 13.5 °—∫ 11.5 g/dL æ∫ primary end point (death, myocardial infarction, CVA, hospitalization for heart failure) √âÕ¬≈– 17.5 „π°≈ÿà¡∑’Ë Hb  ßŸ ·µàæ∫‡æ’¬ß√âÕ¬≈– 13.5 „π°≈ÿà¡∑’Ë Hb µË”°«à“ ‚¥¬§ÿ≥¿“æ™’«‘µ‰¡à ·µ°µà“ß°—π ®“° Normal Hematocrit Trial ‚¥¬ Besarab ·≈–§≥– »÷°…“„πºŸâªÉ«¬øÕ°‡≈◊Õ¥∑’Ë¡’ cardiovascular event ‡ª√’¬∫‡∑’¬∫ Hct √âÕ¬≈– 42 °—∫√âÕ¬≈– 30 æ∫«à“°≈ÿà¡∑’Ë Hct  Ÿß°«à“¡’Õ—µ√“°“√‡ ’¬ ™’«‘µ·≈– myocardial infarction ¡“°°«à“ RR 1.3 (95% CI 0.9-1.9) ¡’ªí≠À“ vascular access ¡“°°«à“ ‚¥¬ æ∫√âÕ¬≈– 39 ‡∑’¬∫°—∫ √âÕ¬≈– 29 „π°≈ÿà¡∑’Ë Hct µË”°«à“ ∑—Èß 2 °≈ÿà¡¡’Õ—µ√“°“√‡°‘¥ heart failure ∑’˵âÕ߇¢â“ √—∫°“√√—°…“„π‚√ß欓∫“≈‰¡à·µ°µà“ß°—π14 ®“° observational study ‚¥¬ Regedor DL ·≈–§≥– æ∫«à“¡’§«“¡ —¡æ—π∏å√–À«à“ß Hb °—∫ cardiovascular mortality „π incident ·≈– prevalent hemodialysis ‡ªìπ·∫∫ J-shaped ‡¡◊ËÕ„™â Hb 11.5-12 g/ dl ‡ªìπ reference æ∫«à“ risk of CVD mortality µË” ÿ¥∑’Ë Hb 12-13 g/dL ·≈–‡æ‘Ë¡¢÷Èπ∑’Ë Hb range 11-11.5 ·≈– ¡“°°«à“ 13.5 g/dL20 ·≈–„π°“√»÷°…“ ACORD Anemia Correction in Diabetes æ∫«à“ºŸâªÉ«¬‡∫“À«“π∑’ˉ¥â√—∫ erythropoietin ®π¡’ Hb 13-15 g/dL ¡’§ÿ≥¿“æ™’«‘µ¥’°«à“ºâŸªÉ«¬∑’ˉ¥â√—∫°“√√—°…“‡¡◊ËÕ Hb πâÕ¬°«à“ 10.5g/ dL ·µà‰¡à¡’§«“¡·µ°µà“ß°—π„π left ventricular mass index ∑’Ë 15 ‡¥◊Õπ13 ®–‡ÀÁπ‰¥â«à“·¡â¿“«–´’¥®–¡’º≈‡ ’¬µàպ⟪ɫ¬‰µ«“¬‡√◊ÈÕ√—ß °“√·°â‰¢¿“«–´’¥¡’ª√–‚¬™πå ·µà Hb ∑’ˠߟ ‰¡à‰¥â¡’º≈¥’‡ ¡Õ‰ª„πºâŸªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß ®“° meta-analysis æ∫«à“°≈ÿࡺŸâªÉ«¬∑’Ë¡’ target Hb  Ÿß ‡∑’¬∫°—∫ºâŸªÉ«¬∑’Ë¡’ Hb µË”°«à“ ®–¡’ risk of all-cause mortality  Ÿß¢÷Èπ RR 1.17 (95% CI 1.01-1.35), risk for vascular access thrombosis RR 1.34 (95%CI 1.16-1.54), risk of poor controlled blood pressure RR 1.27 (95%CI 1.08-1.5) ‚¥¬ incidence of myocardial infarction ‰¡à·µ°µà“ß°—π21 ®“°¢âÕ¡≈Ÿ ∑’Ë¡’°“√»÷°…“ª√–‚¬™πå¢Õß°“√·°â‰¢¿“«–´’¥®π¡’ Hb  Ÿß ‚¥¬‡©æ“–¡“°°«à“ 13- 13.5 g/dL ¡—°‡ªìπ„π·ßà§ÿ≥¿“æ™’«‘µ ·µàº≈µàÕÀ—«„®À√◊ÕÕ—µ√“°“√‡ ’¬™’«‘µ¡—°‰¡à‰¥âº≈¥’™—¥‡®π §”·π–π” „π°“√¥·Ÿ ≈ºâŸªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß„π¢≥–π’È ¡—°µ—Èß target Hb ‰«âª√–¡“≥ 12 g/dL ‡™àπ„π FDA À√◊Õ DOQI ·π–π”„Àâ target Hb 11-12 g/dL ‰¡à§«√‡°‘π 13 g/dL  ”À√—∫ EBPG „Àâ target Hb ¡“°°«à“ 11 g/dL ·µà‰¡à ‡°‘π 12 g/dL ¬°‡«âπ„πºâŸªÉ«¬ severe cardiovascular disease ∑’ˬ—ß¡’Õ“°“√¢Õß angina ‡¡◊ËÕ Hb ∂÷ß 12 g/dL ·≈â« À√◊Õ„πºŸâªÉ«¬ COPD Õ¬à“߉√°Áµ“¡ target π’ȉ¡à„™à ”À√—∫ºŸâªÉ«¬∑’ˉ¥â√—∫‡≈◊Õ¥‡æ◊ËÕ√—°…“¿“«–´’¥22 168

Current Management of Anemia in Dialysis Patients  ”À√—∫ target Hb „πºâŸªÉ«¬≈â“߉µ∑“ß™àÕß∑âÕß ¬—߉¡à¡’¢âÕ¡Ÿ≈«à“§«√·µ°µà“ß®“°ºŸâªÉ«¬øÕ° ‡≈Õ◊ ¥ ¥ß— ππ—È „™â target ‡¥¬’ «°π— „π°“√¥·Ÿ ≈·µ¡à ¢’ Õâ ¥„’ πºªâŸ «É ¬≈“â ߉µ∑“ß™Õà ß∑Õâ ß∑¡’Ë °— µÕâ ß°“√erythropoietin „π¢π“¥∑’˵˔°«à“23 °“√√—°…“¿“«–´’¥„πºâŸªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß ‰¥â·°à °“√„™â erythropoietic-stimulating agent, °“√ „™â adjuvant therapy ·≈–°“√„À‡â ≈Õ◊ ¥ °“√∑” dialysis ‡Õß°‡Á ªπì °“√√°— …“¿“«–‰µ«“¬‡√ÕÈ◊ √ß— ∑¡Ë’ º’ ≈µÕà ¿“«– ´’¥‡™àπ°—π 5. °“√„™â Erythropoietic-stimulating agent (ESA) ‡¥‘¡°“√√—°…“¿“«–´’¥„πºŸâªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß „™â°“√„Àâ‡À≈Á° folate ·≈–„Àâ‡≈◊Õ¥‡¡◊ËÕ¡’Õ“°“√ Õ’°∑—Èß¡’°“√„™â androgenic steroid „π°“√°√–µÿâπ erythropoiesis ·µà°“√√—°…“‡À≈à“π’È¡’ª√– ‘∑∏‘¿“扡॒ ·≈–∑ ’Ë ”§≠— §Õ◊ ¡º’ ≈¢“â ߇§¬’ ߧÕà π¢“â ß¡“°√«¡∑ß—È °“√√°— …“∫“ßÕ¬“à ߇™πà °“√„À‡â ≈Õ◊ ¥¡º’ ≈µÕà °“√«“ß·ºπ °“√√—°…“‚¥¬°“√ª≈°Ÿ ∂à“¬‰µ„πÕ𓧵 ‡πÕ◊Ë ß®“°æ¬“∏°‘ ”‡π¥‘ À≈°— ¢Õß¿“«–´¥’ „πºªâŸ «É ¬‰µ«“¬‡√Õ◊È √ß— ‡ªπì °“√¢“¥erythropoietin (epo) À√◊Õ¡’‰¡à‡æ’¬ßæÕ ‡π◊ËÕß®“°¡’°“√∑”≈“¬ normal renal microvasculature ∑”„Àâ√∫°«π adequate oxygen sensing, ¡’°“√‡ª≈’ˬπ·ª≈ߢÕß peritubular oxygen pressure ‡°‘π√–¥—∫∑’Ë®–°√–µÿâπ°“√À≈—Ëß epo ∑’Ë‡æ’¬ß æÕ, ¡’ transformation ¢Õß epo-producing renal peritubular, fibroblast-like cell ‡ªìπ matrix-producing myofibroblast ·≈– ¡’°“√∑”≈“¬ paracrine signal ®“° interstitial ·≈– epithelial cell ∑’ËÕ¬Ÿà¢â“߇§’¬ß „πªï 1983 ‰¥â¡’°“√ clone human erythropoietin gene ‰¥â ”‡√Á® recombinant test „π —µ«å ∑¥≈Õß‚¥¬ Amgen corporation „πªï 1984, 1985 ·≈–‰¥â¡’√“¬ß“π clinical trial ∑’Ëπ”¡“„™â√—°…“ºŸâªÉ«¬‡ªìπ §√—Èß·√°„πªï 1986 ®“°π—Èπ‰¥â¡’°“√æ—≤π“·≈–𔉪„™âÕ¬à“ß·æ√àÀ≈“¬ 2 Erythropoietin ‡ªìπ glycoprotein ∑’Ë √â“ß®“° endothelial cell ∑’Ë peritubular capillary „π cortex ·≈– outer medulla ¢Õ߉µ epo gene ·¬°‰¥â®“° human fetal liver genomic library ´÷Ëß gene π’È Õ¬àŸ∫π long arm ¢Õß chromosome 7  √â“ß‚¥¬Õ“»—¬ chinese hamster ovary cell (CHO) ∑’Ë∂Ÿ° transfect ¥â«¬ epo- containing plasmid epo gene π’È®– encode 193 amino acid ·≈–¡’ posttranslation modification ‚¥¬°“√ remove c-terminal amino acid  à«π functional protein ®–ª√–°Õ∫¥â«¬ 2 internal sulfide bonds √–À«à“ß cysteines ·≈– linkage to 4 carbohydrate chain ´÷Ëß¡’ 3 N-linked to asparagine ∑’˵”·Àπàß 24, 38, 83 ·≈– o-linked to serine ∑’˵”·Àπàß 126 9 Epo ®–®—∫°—∫ extracellular domain ¢Õß epo receptor ·≈–‡°‘¥ signaling À≈—ß®“°∑’Ë¡’ dimerization ¢Õß 2 monomers ´÷Ëß epo receptor π’È¡’¡“°∑’Ë CFU-E ·≈– pronormoblastic stage  à«π reticulocyte ·≈– mature red blood cell ®–‰¡à¡’ receptor π’È πÕ°®“°π’Ȭ—ßæ∫ receptor π’ȉ¥â∑’Ë non- hematopoietic cell ‡™àπ neuronal cell, cardiomyocyte, vascular cell ·≈– renal tubular cell ‡¡Õ◊Ë epo ®∫— °∫— epo receptor ®–¡º’ ≈¬∫— ¬ß—È programmed cell death ∑”„À®â ”π«π¢Õß apoptotic erythroid progenitor ≈¥≈ß ¡’°“√ √â“ß·≈–‡°‘¥ maturation ¢Õ߇¡Á¥‡≈◊Õ¥·¥ß 24,25 169

Practical Dialysis in the Year 2009 º≈ antiapoptotic π’ȇ°‘¥ºà“π∑“ß 1. °“√°√–µπâÿ transcription gene ∑Ë’ encode antiapoptotic molecule ‰¥·â °à Bcl-XL, XIAP, GIAP2 2. ¬—∫¬—Èß transcription ¢Õß gene ∑’Ë encode proapoptotic molecule ‡™àπ Fas ligand, Bim 3. °√–µÿâπ protein kinase B/Akt 4. induce HSP 70 endogenous epo ª√–°Õ∫¥â«¬ 4 polypeptide core ∑’Ë¡’ 165 amino acids ¡’ 4 glycosylation sites §◊Õ 3 N-linked ·≈– 1 0-linked oligosaccharide chain ´÷Ëß isoforms ®–·µ°µà“ß°—π∑’Ë 4 glycan residues 3 N-linked carbohydrate chain Õ“®ª√–°Õ∫¥«â ¬ 2-4 oligosaccharide branches ´ß÷Ë ·µ≈à – branch ®–¡’ negative charged sialic acid  à«π O-linked sugar chain ¡’ 2 sialic acid residues ®”π«π¢Õß sialic acid residue π’È®–∫àß∂÷ß net negative charge ¢Õß‚¡‡≈°ÿ≈ bioavailability ·≈– fate ¢Õß epo ¢÷Èπ°—∫ N-linked carbohydrate residues „πÀπŸ æ∫«à“ erythropoietin isoform ∑’Ë¡’®”π«π sialic acid residue ¡“° ®–¡’ negative charge ¡“° ∑”„Àâ∂°Ÿ °”®—¥®“° °√–· ‡≈◊Õ¥™â“°«à“ ∑”„Àâ¡’ half-life ¬“«°«à“ ·≈–¡’ in vivo efficacy  ßŸ °«à“ °“√∑”≈“¬ epo ®“°°√–· ‡≈Õ◊ ¥ ‡°¥‘ ‚¥¬«∏‘ ’ hepatic uptake, renal clearance ·≈– epo-receptor mediated uptake ‡¢â“‰ª„π‡´≈≈å ·≈–‡°‘¥ intracellular degradation °“√®—∫°—∫ epo receptor ¡’§«“¡ ”§—≠ µàÕ°“√ clearance ‚¥¬ epo isoform ∑’Ë®—∫°—∫ receptor ‰¥âµË” ®–∂°Ÿ clearance ‰¥â™â“ ∑”„Àâ¡’ half-life ¬“« πÕ°®“°π’È®“°°“√»÷°…“æ∫«à“„πºŸâªÉ«¬‚√§µ—∫ ‰¡à¡’°“√‡ª≈’ˬπ·ª≈ߢÕß°“√ clearance ¢Õß epo √«¡ ∑—Èß„πºŸâªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß °“√ clearance ‰¡à·µ°µà“ß®“°§πª°µ2‘ 5 Erythropoietic stimulating agent (ESA) ‡ªπì  “√∑ Ë’ “¡“√∂‡æ¡Ë‘ °“√ √“â ߇¡¥Á ‡≈Õ◊ ¥·¥ß ‚¥¬Õ“® ¡º’ ≈‚¥¬µ√ßÀ√Õ◊ ∑“ßÕÕâ ¡µÕà epo receptor ª®í ®∫ÿ π— ∑¡’Ë „’ ™‡â ªπì recombinant human erythropoietin ´ß÷Ë ª√–°Õ∫ ¥â«¬ amino acid sequence ∑’ˇÀ¡◊Õπ endogenous epo ·µà¡’ —¥ à«π¢Õß sialated acidic carbohydrate residue ¡“°°«à“ endogenous epo 5.1 ™π¥‘ ·≈–§ÿ≥ ¡∫—µ¢‘ Õß ESA ¥—ßµ“√“ß∑’Ë 1 1. epoetin-α 2. epoetin-β 3. epoetin-ω 4. epoetin-δ 5. epoetin analogue 5.2 §«“¡·µ°µà“ߢÕß ESA ·µà≈–™π‘¥  ”À√—∫ epoetin-α ·≈– epoetin-β  √â“ß®“° Chinese hamster ovary cell ∑’Ë transfect ¥â«¬ authetin human epo gene epoetin-β ¡’ molecular wt. ¡“°°«à“ epoetin-alpha ·≈–¡’®”π«π sialated glycan residue πâÕ¬°«à“ epoetin-α ·≈–¡’ in vivo / in vitro bioactivity ratio ¡“°°«à“ epoetin-α √âÕ¬≈– 20 ®“°°“√»÷°…“„πºâŸ™“¬Õ“¬ÿπâÕ¬ ∑’Ë¡’ ÿ¢¿“æ·¢Áß·√ß 18 §π æ∫«à“ epoetin-β ‡¡◊ËÕ„Àâ Intravenous (IV) À√◊Õ 170

Current Management of Anemia in Dialysis Patients µ“√“ß∑’Ë 1 ‡ª√’¬∫‡∑’¬∫§ÿ≥ ¡∫—µ‘¢Õß epoetin25 subcutaneous route (sc) ¡’ terminal elimination half-life ¬“«°«à“ epoetin-α ·≈–‡¡◊ËÕ„Àâ sc epoetin-β ¡’ delayed absorption °«à“ epoetin-α ·≈–¡’º≈∑”„À⇰‘¥ reticulocytosis ¡“°°«à“ epoetin-α ·µà‡¡◊ËÕ∑”°“√ »°÷ …“„πºªâŸ «É ¬‰µ«“¬‡√ÕÈ◊ √ß— ∑‰Ë’ ¥√â ∫— °“√√°— …“¥«â ¬°“√øÕ°‡≈Õ◊ ¥À√Õ◊ ≈“â ߉µ∑“ß™Õà ß∑Õâ ß æ∫«“à half-life ‰¡à ·µ°µà“ß°—π Õ“®‡æ√“– pharmacokinetic property ¢Õß epoetin-β counterbalance °—∫º≈¢Õß sialylation ∑’Ë ¡’µàÕ pharmacokinetic ¢Õ߬“ ∑”„Àâ§à“ half-life ‰¡à·µ°µà“ß°—π epoetin-ω  √â“ß®“° baby hamster kidney cell ‚§√ß √â“ß¡’√âÕ¬≈– 60 ‡ªìπ O-glycosylated ∑’Ë serine residue 126 ·≈–¡’ major oligosaccharide structure ‡ªìπ tetra-antennary type ∑’Ë carbohydrate residues ¡’ tetrasialylated 1 „π N-glycosylation site ª√–°Õ∫¥â«¬ phosphorylated oligomannosidic side chain ´÷Ëß‚§√ß √â“ßπ’È∑”„Àâ¡’§«“¡·µ°µà“ß„π·ßà pharmacokinetic ®“° epo µ—«Õ◊Ëπ ¡’°“√»÷°…“‡≈Á°Ê æ∫ «à“ epoetin-ω potent °«à“ epoetin-α epoetin-δ ‡ªìπ gene-activated erythropoietin À√◊Õ dynepoTM  √â“ß®“° human cell ∑’Ë∂°Ÿ genetic engineered „Àâ transcribe ·≈– translate epo gene ¿“¬„µâ newly introduced regularly DNA sequence ‰¥â√—∫°“√ approve „π¬ÿ‚√ª epoetin analogue À√◊Õ darbepoetin-α  √â“ß„π CHO cell ‡ªìπ hyperglycosylated epo analogue ∑’Ë¡’ prolonged survival „π°√–· ‡≈◊Õ¥ ·≈– bioactivity  Ÿß°«à“ epo ‡π◊ËÕß®“°¡’ amino acid sequence ∑’Ë ·µ°µà“ß®“° endogenous epo ∑’Ë 5 µ”·Àπàß ·≈–¡’°“√‡µ‘¡ 2 N-linked oligosaccharide ∑’Ë asparagines residue „πµ”·Àπàß 30, 88 ‚¥¬‰¡à∑”≈“¬ conformation ∑”„Àâ®—∫°—∫ epo receptor ‰¥âµË” ·µà°“√¡’ sialic acid ¡“° ∑”„Àâ¡’ half-life ‡ªìπ 3 ‡∑à“¢Õß IV epoetin-α (25.3 ‡∑’¬∫°—∫ 8.5 ™¡.)26 time to peak ‡¡◊ËÕ„Àâ sc „πºâŸªÉ«¬≈â“߉µ∑“ß™àÕß∑âÕß 54 ™¡.  ”À√—∫ darbepoetin-α ‡∑’¬∫°—∫ 16-24 ™¡.  ”À√—∫ epoetin-α ®“°°“√»÷°…“„πÀπŸæ∫«à“ darbepoetin-α ‰¡à«à“®–„Àâ IV À√◊Õ sc 3 §√—ÈßµàÕ —ª¥“Àå potent °«à“ epoetin-α 171

Practical Dialysis in the Year 2009 3.6 ‡∑à“25 πÕ°®“°π’È®“°°“√»÷°…“¢Õß Locatelli F ·≈–§≥– ¬—ßæ∫«à“ darbepoetin-α °“√„Àâ IV À√◊Õ sc ¢π“¥∑’Ë„™â‰¡à·µ°µà“ß°—π 27 Continuous erythropoiesis receptor activator (CERA) ‡ªìπ ESA ∑’ˇ√‘Ë¡¡’°“√»÷°…“·≈–π”¡“ „™â∑“ߧ≈‘π‘° ‚§√ß √â“ߪ√–°Õ∫¥â«¬ protein core, methoxy-polyethylene glycol polymer, succidinmidyl butanoic acid linker ¡’πÈ”Àπ—°‚¡‡≈°ÿ≈ 60,000 dalton ®“°°“√»÷°…“ in vitro æ∫«à“ CERA ·¬°µ—«ÕÕ°®“° epo receptor ‰¥â‡√Á«°«à“ epoetin-β ∑”„Àâ¡’º≈°√–µÿâπ cell proliferation ‰¥âπâÕ¬°«à“ epoetin-β ·µà‡¡◊ËÕ»÷°…“ „π normocythaemic mice æ∫«à“ CERA  “¡“√∂°√–µÿâπ„Àâ¡’®”π«π reticulocyte ‰¥â¡“°°«à“ epoetin-β · ¥ß«à“ CERA °√–µÿâπ erythroid progenitor cell ‰¥â¡“°°«à“ epoetin-β §‘¥«à“‡ªìπ‡æ√“– √–¬–‡«≈“∑’Ë CERA ®∫— °∫— epo receptor  π—È ‡°π‘ °«“à ∑®’Ë –‡°¥‘ internalization ∑”„À‡â °¥‘ repeated cycle of receptor binding, stimulation ·≈– dissociation ´÷Ëß®“° pharmacokinetic study æ∫«à“ CERA ¡’ systemic clearance πâÕ¬ °«à“ epoetin Õ◊Ëπ ∑”„Àâ¡’ half-life ¬“«°«à“ 2-7 ‡∑à“25 ®“°°“√»÷°…“ phase I æ∫«à“ CERA ¡’ half-life 130 ™¡. ‰¡à¢÷Èπ°—∫ route ∑’Ë„Àâ „π phase II »÷°…“„πºŸâªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß ∑—Èß∑’Ë dialysis ·≈–¬—߉¡à‰¥â dialysis æ∫«à“ CERA  “¡“√∂·°â‰¢¿“«–´’¥‰¥â ‡¡◊ËÕ„Àâ∑ÿ° 2  —ª¥“Àå ·≈– “¡“√∂ maintain Hb ‰¥â‡¡◊ËÕ„Àâ∑ÿ° 1 ‡¥◊Õπ „π phase III æ∫«à“ CERA ∑’Ë„Àâ∑ÿ°‡¥◊Õπ  “¡“√∂ maintain Hb „Àâ§ß∑’ˉ¥â „πºâŸªÉ«¬ dialysis ∑’Ë ‡ª≈’Ë¬π®“°‡¥‘¡„™â epoetin À√◊Õ darbepoetin-α 28 °“√µ¥—  π‘ „®‡≈Õ◊ °„™â ESA „πºªŸâ «É ¬‰µ«“¬‡√Õ◊È √ß— ∑¡’Ë ¿’ “«–´¥’ §«√§”πß÷ ∂ß÷ ™π¥‘ ¢Õß ESA, ¢π“¥ ∑’ˇ√‘Ë¡„™â, route ∑’Ë„Àâ ·≈–§«“¡∂’Ë„π°“√„Àâ, °“√µ‘¥µ“¡·≈–ª√–‡¡‘π°“√µÕ∫ πÕß, °“√ª√—∫¢π“¥∑’Ë„™â, º≈¢â“߇§’¬ß ·≈–‡π◊ËÕß®“° ESA ¡’√“§“·æß ¥—ßπ—Èπªí®®—¬∑“߇»√…∞∞“π–  ‘∑∏‘„π°“√√—°…“®÷߇ªìπªí®®—¬  ”§—≠„π°“√æ‘®“√≥“‡≈◊Õ°„™â 5.3 °“√‡≈Õ◊ °™π¥‘ ¢Õß ESA ESA ∑’Ë¡’°“√π”¡“„™â„πªí®®ÿ∫—π ‰¥â·°à epoetin-α, epoetin-β, darbepoetin-α ·≈– CERA ´÷Ëß epoetin-α ·≈– epoetin-β ¡’§ÿ≥ ¡∫—µ‘∑“ß pharmacokinetic ‡À¡◊Õπ°—π ·≈–∂◊Õ«à“‡ªìπ°≈ÿà¡ short-acting ‡¡◊ËÕ‡∑’¬∫°—∫ darbepoetin-α ·≈– CERA29 ®“°°“√»÷°…“‚¥¬ Tolman ·≈–§≥– „πºŸâªÉ«¬øÕ°‡≈◊Õ¥ æ∫«à“‡¡◊ËÕ‡ª≈’Ë¬π®“° epoetin-β 2- 3 §√—ÈßµàÕ —ª¥“Àå ‰ª‡ªìπ darbepoetin-α sc 1 §√—ÈßµàÕ —ª¥“Àå ‡ª√’¬∫‡∑’¬∫°—∫ epoetin-β sc 1 §√—ÈßµàÕ  —ª¥“Àå ‚¥¬ —¥ à«π°“√ª√—∫¢π“¥√–À«à“ß epoetin-β °—∫ darbepoetin-α ‡∑à“°—∫ 200 IU: 1 µg æ∫«à“∑’Ë 1 ‡¥◊Õπ °≈ÿà¡∑’ˇª≈’Ë¬π‰ª„™â darbepoetin-α sc 1 §√—ÈßµàÕ —ª¥“Àå  “¡“√∂≈¥¢π“¥¬“≈ß ®“° 0.59 µg/kg/ week ‡ªìπ 0.46 µg/kg/week, p=0.002 ·≈–‡¡◊ËÕ‡ª√’¬∫‡∑’¬∫¢π“¥¢Õß epoetin-β æ∫«à“µâÕß„™â¡“°°«à“ ¢π“¥¢Õß darbepoetin-α √âÕ¬≈– 4430 ®“°°“√»÷°…“ AMICUS Anemia Correction and Sustained Maintenance in Dialysis »÷°…“ ‡ª√’¬∫‡∑’¬∫ efficacy √–À«à“ß CERA IV ∑ÿ° 2  —ª¥“Àå °—∫ epoetin-α, epoetin-β IV 3 §√—ÈßµàÕ —ª¥“Àå æ∫ «à“°“√µÕ∫ πÕߢÕß∑—Èß 2 °≈ÿà¡„π°“√‡æ‘Ë¡¢Õß Hb ∑’Ë 24  —ª¥“À剡෵°µà“ß°—π §◊Õ √âÕ¬≈– 93.3 ·≈– 91.3 µ“¡≈”¥—∫ ‚¥¬ median time to response ª√–¡“≥ 8  —ª¥“Àå ´÷Ë߇ª√’¬∫‡∑’¬∫∑’Ë¡’°“√»÷°…“Õ—µ√“ 172

Current Management of Anemia in Dialysis Patients °“√µÕ∫ πÕß∑’Ë 20  —ª¥“Àå „πºâŸªÉ«¬∑’ˉ¥â darbepoetin-a ‡æ’¬ß√âÕ¬≈– 7228 ·≈–®“°°“√»÷°…“ MAXIMA Maintenance of hemoglobin excels with intravenous administration of CERA „πºŸâªÉ«¬ dialysis 517 √“¬ ‡ª√’¬∫‡∑’¬∫°“√‰¥â√—∫ CERA IV ∑ÿ° 2  —ª¥“Àå ·≈– ∑ÿ° 1 ‡¥◊Õπ °—∫°“√„™â epoetin 1-3 §√—ÈßµàÕ —ª¥“Àå æ∫«à“º≈°“√µÕ∫ πÕߢÕß∑—Èß 3 °≈ÿࡉ¡à·µ°µà“ß°—π31 ·¡«â “à ESA ·µ≈à –µ«— Õ“®¡’ potency ·µ°µ“à ß°π— ·µÕà ¬“à ߉√°µÁ “¡ ¬ß— ‰¡¡à ¢’ Õâ ¡≈Ÿ «“à ESA ·µ≈à – ™π‘¥·µ°µà“ß°—π„π·ßà¢Õß°“√·°â‰¢¿“«–´’¥25 Õ“®¡’ªí≠À“„π°“√„™â long acting epoetin ∑’Ë Hb ®–≈¥≈ß ™â“À≈—ßÀ¬ÿ¥¬“„π°√≥’∑’Ë Hb  ßŸ ‡°‘π‰ª32 5.4 Route ∑’Ë„À⬓ ESA DOQI ‰¥·â π–π” route ∑®Ë’ –„À¬â “ ‚¥¬æ®‘ “√≥“®“° √–¬–¢Õ߉µ«“¬‡√ÕÈ◊ √ß— , treatment setting, efficacy ·≈– class of ESA ∑’Ë„™â °“√„Àâ ESA „πºŸâªÉ«¬øÕ°‡≈◊Õ¥ “¡“√∂„À≥â∑—Èß∑“ß IV ·≈– sc ·µà„πºâŸ ªÉ«¬≈â“߉µ∑“ß™àÕß∑âÕß ´÷Ë߉¡à¡’ vascular access °“√„Àâ∑“ß IV ®–‰¡à –¥«°‡¡◊ËÕ‡∑’¬∫°—∫°“√„Àâ‚¥¬ sc ·µà ”À√—∫°“√„Àâ epoetin-α sc „πºŸâªÉ«¬øÕ°‡≈◊Õ¥ „π∫“ߪ√–‡∑»¢Õ߬ÿ‚√ª ·≈– FDA ‰¡à·π–π”°“√„Àâ «‘∏’π’È ‡π◊ËÕß®“°¡’√“¬ß“π —¡æ—π∏å°—∫°“√‡°‘¥ pure red cell aplasia33 „π°“√„Àâ short-acting ESA ∑“ß IV ¡’ half-life πâÕ¬°«à“ 8 ™¡. ·≈–√–¥—∫¬“„π°√–· ‡≈◊Õ¥ ®–°≈—∫‡¢â“ Ÿà baseline ¿“¬„π 24 ™¡.  à«π°“√„À⬓ sc ¡’ half-life 24-30 ™¡. √–¥—∫¬“„π°√–· ‡≈◊Õ¥‡ªìπ 2 ‡∑à“¢Õß baseline ‰¥âπ“π 55 ™¡.2 ¥—ßπ—Èπ°“√„À⬓ sc ·¡â«à“®–¡’ bioavailability ‡æ’¬ß 1 „π 3 ¢Õß IV dose ·µà°“√»÷°…“ à«π¡“° æ∫«à“ °“√„À⬓ sc „™â¢π“¥µË”°«à“ IV °“√„™â¬“ sc  “¡“√∂≈¥¢π“¥¢Õß ¬“∑’Ë„™â√âÕ¬≈– 15-50 ¢Õß IV ·¡â¡’∫“ß√“¬ß“π«à“¢π“¥¬“∑’Ë„™â∑“ß IV ·≈– sc ‰¡à·µ°µà“ß°—π À√◊Õ„™â ¢π“¥¬“‡æ‘Ë¡¢÷Èπ„π°“√‡ª≈’Ë¬π®“°°“√„À⬓ IV ‡ªìπ sc °“√∑’Ë sc  “¡“√∂≈¥¢π“¥¬“‰¥â Õ“®‡π◊ËÕß®“° °“√„À⬓∑“ß sc ¡’ half-life ¢Õ߬“π“π°«à“ ∑”„Àâ¡’ sustained stimulation ¢Õß erythroid progenitor cell ·≈–°“√∑’Ë√–¥—∫¬“ epo „π°√–· ‡≈◊Õ¥≈¥≈߇√Á«‡¡◊ËÕ„Àâ∑“ß IV Õ“®∑”„Àâ¡’°“√·µ°¢Õ߇¡Á¥‡≈◊Õ¥·¥ßµ—« ÕàÕπ ¥—ßπ—Èπ∑”„Àâ°“√„À⬓ sc ®÷ß¡’ efficacy ¡“°°«à“ IV ®“°°“√»÷°…“ meta-analysis 27 °“√»÷°…“ ¡’ ºâŸªÉ«¬ 916 √“¬ æ∫«à“‡¡◊ËÕ„Àâ epoetin sc ¢π“¥¬“®–πâÕ¬°«à“ IV 50 IU/kg/week ·≈– “¡“√∂ª√–À¬—¥ ‡ß‘π‰¥â√âÕ¬≈– 30 ·≈–®“°°“√»÷°…“‚¥¬ Kaufman J ·≈–§≥– „πºâŸªÉ«¬øÕ°‡≈◊Õ¥ 208 √“¬„π 24 hemodialysis center æ∫«à“°≈ÿà¡∑’ˉ¥â epoetin sc ®–¡’¢π“¥¬“∑’Ë„™â‡©≈’ˬµàÕ —ª¥“Àå πâÕ¬°«à“°“√„À⬓∑“ß IV √âÕ¬≈– 32 §◊Õ°“√„Àâ sc „™â¬“¢π“¥‡©≈’ˬ 95.1±75 IU  à«π°“√„À⬓ IV „™â¬“‡©≈’ˬ 140.3±88.5 IU, p<0.00134 ·µà®“° ESAM study 1998 (European Survey on Anemia Management) æ∫«à“°“√„Àâ sc °—∫ IV ¢π“¥¬“∑’Ë„™âµà“ß°—π‡æ’¬ß 9 IU/kg/week (p=ns) ·µà√“¬ß“ππ’ȇªìπ retrospective study ·≈– „™â target Hb ·µ°µà“ß°—π25 ®“°√“¬ß“π¢Õß ESAM „πªï 2003 æ∫«à“„πºŸâªÉ«¬∑’Ë¡’ Hb πâÕ¬°«à“ 11 g/dL ¢π“¥ ‡©≈’ˬ¢Õß epoetin ∑’Ë„Àâ∑“ß sc πâÕ¬°«à“°“√„Àâ IV Õ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘µ‘ ·µà∂â“„π°≈ÿࡺ⟪ɫ¬∑’Ë¡’ Hb ¡“°°«à“ 11 g/dL ¢π“¥¬“‡©≈’ˬ¢Õß∑—Èß 2 route ‰¡à·µ°µà“ß°—π35  ”À√—∫°“√„À⬓ ESA ™π‘¥ long acting darbepoetin-α æ∫«à“„πºŸâªÉ«¬øÕ°‡≈◊Õ¥ À√◊Õ≈â“߉µ ∑“ß™àÕß∑âÕß ¢π“¥¬“∑’Ë„™â‰¡à«à“®–„À⬓∑“ß IV À√◊Õ sc ‰¡à·µ°µà“ß°—𠇙àπ‡¥’¬«°—∫ CERA ´÷Ëß¡’ half-life ª√–¡“≥ 130 ™¡.25 173

Practical Dialysis in the Year 2009 °“√„À⬓∑“ß sc °—∫ IV ¬—ß¡’§«“¡·µ°µà“ß„π·ßàº≈¢â“߇§’¬ß∑’ˇ°‘¥®“°°“√©’¥ ‚¥¬‡©æ“– Õ“°“√ª«¥µ√ßµ”·Àπßà ∑©’Ë ¥’ ∑æ’Ë ∫„π°“√„À¬â “sc ·µ°à  Á “¡“√∂≈¥Õ“°“√ª«¥‰¥‚â ¥¬°“√º ¡ benzyl alcohol À√◊Õ°“√„™â phosphate-buffered epoetin-α ´÷Ëß∑”„À⇰‘¥Õ“°“√ª«¥πâÕ¬°«à“ citrate-buffered25 °“√„À⬓ ESA ∑“ß intraperitoneal (IP) „πºŸâªÉ«¬≈â“߉µ∑“ß™àÕß∑âÕß æ∫«à“¡’ªí≠À“ bioavailability ‰¡à¥’ ‚¥¬‡©æ“–‡¡◊ËÕº ¡°—∫πÈ”¬“ dialysate ·µà¡’∫“ß°“√»÷°…“√“¬ß“π«à“ bioavailability ¥’ ‰¡à·µ°µà“ß®“°°“√„À⬓ sc ∂â“„ à„π™àÕß∑âÕߢ≥–‰¡à¡’πÈ”¬“ dialysate „π™àÕß∑âÕß Õ¬à“߉√°Áµ“¡ EBPG °Á‰¡à·π–π”„À⬓∑“ß IP 33 5.5 §«“¡∂„Ë’ π°“√„À¬â “ ESA °“√„À⬓ ESA ¡’ 2 phase §◊Õ„π™à«ß·√°‡ªìπ correction phase ™à«ßµàÕ¡“‡ªìπ maintenance phase §«“¡∂’Ë„π°“√„À⬓ ¡—°æ‘®“√≥“®“° half-life ¢Õ߬“ ¬“°≈ÿà¡ epoetin-α ·≈– epoetin-β ‡ªìπ short-acting ¡—°„À⬓ 2-3 §√—ÈßµàÕ —ª¥“Àå ·µà¡’∫“ß°“√»÷°…“∑’Ë„À⬓‡æ’¬ß 1 §√—ÈßµàÕ —ª¥“Àå ·µà‚¥¬À≈—° °“√·≈«â °“√„À¬â “‡æ¬’ ß 1 §√ß—È µÕà  ª— ¥“Àπå “à ®–¥Õâ ¬°«“à ‡πÕ◊Ë ß®“°„πºªŸâ «É ¬‰µ«“¬‡√Õ◊È √ß— ®–¡’ critical plasma epo threshold  ”À√—∫ effective erythropoiesis „π™à«ß·√°À≈—ß„À⬓ √–¥—∫¬“ epo „π°√–· ‡≈◊Õ¥ ßŸ ®– ®—∫°—∫ epo receptor ∫π bone marrow progenitor cell ®πÀ¡¥ µàÕ¡“‡¡◊ËÕ receptor available Õ’°§√—Èß ·µà √–¥—∫¬“„π°√–· ‡≈◊Õ¥‰¥â≈¥≈ß·≈â«®÷߉¡à¡’ epo „π°√–· ‡≈◊Õ¥∑’Ë®–°√–µÿâπ receptor ´÷Ëß√–¥—∫ epo „π °√–· ‡≈◊Õ¥®–≈¥≈ߵ˔°«à“ threshold ∑’Ë«—π∑’Ë 4 À≈—ß°“√„À⬓ „π°√≥’∑’Ë„Àâ 1 §√—ÈßµàÕ —ª¥“Àå 25 °“√»÷°…“‚¥¬ Locatelli F ·≈–§≥– „πºŸâªÉ«¬øÕ°‡≈◊Õ¥ ‡¡◊ËÕ„™â epoetin IV 1 §√—ÈßµàÕ —ª¥“Àå æ∫«à“ Hb ¡’§à“≈¥≈ß ·≈–µâÕß„™â¢π“¥¢Õß ESA ‡æ‘Ë¡¢÷Èπ ‚¥¬¡’‡æ’¬ß√âÕ¬≈– 64 ¢Õߺ⟪ɫ¬∑’Ë “¡“√∂§ß √–¥—∫ Hb ¥â«¬«‘∏’ IV 1 §√—ÈßµàÕ —ª¥“À剥â Õ¬à“߉√°Áµ“¡·¡âº≈°“√»÷°…“π’ȉ¡à‰¥â π—∫ πÿπ°“√„™â¬“ IV 1 §√—ÈßµàÕ —ª¥“Àå ·µà°Áæ∫«à“ºŸâªÉ«¬®”π«πÀπ÷Ëß°Á¬—ß “¡“√∂„À⬓‡æ’¬ß 1 §√—ÈßµàÕ —ª¥“À剥â 36  ”À√—∫°“√„À⬓ sc  “¡“√∂„Àâ 1 §√—ÈßµàÕ —ª¥“À剥⠡’°“√»÷°…“„πºâŸªÉ«¬øÕ°‡≈◊Õ¥ °“√„Àâ ¬“ sc 1 §√—ÈßµàÕ —ª¥“Àå ‡¡◊ËÕ‡ª√’¬∫‡∑’¬∫°—∫°“√„Àâ 3 §√—ÈßµàÕ —ª¥“Àå ‰¥âº≈‰¡à·µ°µà“ß°—π„π°“√ maintain Hb √«¡∑—È߉¡à·µ°µà“ß„π·ßà¢Õß¢π“¥¬“ epoetin-β ∑’Ë„™â ¥—ßπ—ÈπÕ“®„™â epoetin-β 1-2 §√—ÈßµàÕ —ª¥“Àå∑“ß sc ‰¥â ·µà epoetin-α sc ‰¡à¬Õ¡√—∫„Àâ„™â„π∫“ߪ√–‡∑»‡æ√“–§«“¡‡ ’ˬߵàÕ°“√‡°‘¥ pure red cell aplasia „πºâŸªÉ«¬≈â“߉µ∑“ß™àÕß∑âÕß °“√„À⬓∑“ß sc ¡’§«“¡ –¥«°°«à“ IV ¡’¢âÕ¡≈Ÿ ®“°°“√»÷°…“ æ∫«à“°“√„À⬓ sc 1 §√—ÈßµàÕ —ª¥“Àå ‰¡à·µ°µà“ß®“°°“√„Àâ 2-3 §√—ÈßµàÕ —ª¥“Àå Frifelt ·≈–§≥– »÷°…“ „πºâŸªÉ«¬≈â“߉µ∑“ß™àÕß∑âÕß 16 √“¬ ∑’ˇ§¬‰¥â epoetin 3 §√—ÈßµàÕ —ª¥“Àå ¡“„Àâ 1 §√—ÈßµàÕ —ª¥“Àå æ∫«à“  “¡“√∂ maintain Hb ‰¥â ¬—ß¡’°“√»÷°…“„πºŸâªÉ«¬≈â“߉µ∑“ß™àÕß∑âÕß 128 √“¬∑’ˇ§¬‰¥â epoetin 2-3 §√—Èß µàÕ —ª¥“Àå ‡ª≈’Ë¬π¡“„Àâ∑ÿ° 1  —ª¥“Àå ‡ª√’¬∫‡∑’¬∫°—∫„Àâ∑ÿ° 2  —ª¥“Àå æ∫«à“ “¡“√∂ maintain Hb ‰¥â ∑—Èß 2 °≈ÿà¡ ·µà„π°≈ÿà¡∑’Ë„À⬓∑ÿ° 2  —ª¥“Àå µâÕß„™â¢π“¥¬“‡æ‘Ë¡¢÷Èπ√âÕ¬≈– 13 37 Cochrane systematic review ‚¥¬ Cody J ·≈–§≥– æ∫«à“°“√„Àâ ESA sc 1 §√—ÈßµàÕ —ª¥“Àå ‰¡à·µ°µà“ß®“°°“√„Àâ 2 À√◊Õ 3 §√—ÈßµàÕ —ª¥“Àå „π°“√ maintain target Hb ∑—Èß„πºŸâªÉ«¬øÕ°‡≈◊Õ¥·≈–≈â“ß ‰µ∑“ß™àÕß∑âÕß ¡’°“√»÷°…“‡≈Á°Ê ∑’Ëæ∫«à“„πºâŸªÉ«¬øÕ°‡≈◊Õ¥ µâÕß„™â¢π“¥¬“¡“°°«à“‡¡◊ËÕ„À⬓ 1 §√—Èß µàÕ —ª¥“Àå 38 174

Current Management of Anemia in Dialysis Patients  ”À√∫— long acting epoetin ¡°’ “√»°÷ …“æ∫«“à °“√„À¬â “ 1 §√ßÈ— µÕà  ª— ¥“À„å πºªâŸ «É ¬øÕ°‡≈Õ◊ ¥ ¡ª’ √– ∑‘ ∏¿‘ “æ·≈–§«“¡ª≈Õ¥¿¬— ‰¡·à µ°µ“à ß®“°°“√„Àâ epoetin-α 3 §√ßÈ— µÕà  ª— ¥“Àå ·≈–°“√„À¬â “§«“¡ ∂’ËπâÕ¬≈ß ‰¡à‰¥â‡æ‘Ë¡§«“¡‡ ’ˬ߄π°“√‡°‘¥ unstable Hb ∑’˵âÕß°“√°“√ª√—∫¢π“¥¬“33 ¡’°“√»÷°…“„πºâŸªÉ«¬ dialysis 54 √“¬∑’ˇ§¬‰¥â darbepoietin-α ∑ÿ° 2  —ª¥“Àå ·≈–‡ª≈’Ë¬π‰ª„Àâ ¬“∑ÿ° 3  —ª¥“Àå ‡ªìπ‡«≈“ 20  —ª¥“Àå ·≈–∂â“ Hb 10-13 g/dL ®–„À⬓≈¥≈߇ªìπ∑ÿ° 1 ‡¥◊Õπ æ∫«à“ 38 √“¬ “¡“√∂‡æ‘Ë¡®π‰¥â target Hb ¥â«¬°“√„À⬓∑ÿ° 3  —ª¥“Àå ·≈– 36 √“¬ ∑’ˉ¥â target Hb ¥â«¬°“√„À⬓ ∑ÿ° 1 ‡¥◊Õπ °“√»÷°…“Õ◊Ëπ∑’Ëæ∫«à“°“√„À⬓Àà“ߢ÷Èπ¡’ª√– ‘∑∏‘¿“æ„π long acting epoetin °“√»÷°…“ ARCTOS Administration of CERA in chronic kidney disease patients to treat anemia with twice monthly schedule »÷°…“°“√„Àâ CERA sc ∑ÿ° 2  —ª¥“Àå „πºâŸªÉ«¬∑’ˬ—߉¡à‡√‘Ë¡≈â“߉µ ‡ª√’¬∫‡∑’¬∫°—∫ darbepoetin- α 1 §√—ÈßµàÕ —ª¥“Àå æ∫«à“ºŸâªÉ«¬¡“°°«à“√âÕ¬≈– 90 ¢Õß∑—Èß 2 °≈ÿà¡  “¡“√∂‰¥â target Hb ∑’Ë 28  —ª¥“Àå 39 °“√»÷°…“ PROTOS study Patient receiving CERA once a month for the maintenance of stable Hb ‡ª√’¬∫‡∑’¬∫°“√„Àâ CERA 1 §√—ÈßµàÕ‡¥◊Õπ ‡∑’¬∫°—∫ 2 §√—ÈßµàÕ‡¥◊Õπ °—∫°“√„Àâ epoetin 1-3 §√—Èß µàÕ —ª¥“Àå æ∫«à“ mean change of Hb „π 3 °≈ÿà¡ ‰¡à·µ°µà“ß°—πÕ¬à“ß¡’π—¬ ”§—≠ · ¥ß«à“°“√„À⬓ ‡æ’¬ß 1 §√—ÈßµàÕ‡¥◊Õπ ¡’ª√– ‘∑∏‘¿“懙àπ°—π ·≈–¬—ß “¡“√∂≈¥°“√©’¥¬“‰¥â 144 §√—ÈßµàÕºŸâªÉ«¬µàÕª4ï 0 º≈ ¢Õß°“√»÷°…“ MAXIMA · ¥ß«à“°“√„Àâ CERA 1 §√—ÈßµàÕ‡¥◊Õπ °Á‰¥âº≈¥’‡™àπ°—π31 °“√„À⬓ 1 §√—ÈßµàÕ —ª¥“Àå ¡’¢âÕ¥’„π·ßà¢Õߧ«“¡ –¥«° Õ“®∑”„Àâ compliance ¥’¢÷Èπ ·≈– ≈¥§à“„™â®à“¬„π°“√√—°…“‰¥â ®“°°“√»÷°…“„π 9 dialysis center „π¬ÿ‚√ª æ∫«à“ºŸâªÉ«¬ dialysis 50 √“¬ ∑’Ë ‰¥â ESA 3 §√—ÈßµàÕ —ª¥“Àå µâÕß°“√·æ∑¬å·≈–欓∫“≈¥·Ÿ ≈ 503 ™¡.µàÕªï ·µà°“√≈¥®”π«π§√—ÈߢÕß°“√ ©’¥¬“‡À≈◊Õ 1 §√—ÈßµàÕ —ª¥“Àå ®– “¡“√∂≈¥®”π«π™¡.‰¥â 350 ™¡.µàÕªï1 ·µàÕ¬à“߉√°Áµ“¡¬—߉¡à¡’¢âÕ¡Ÿ≈¡“°æÕ∑’Ë®– π—∫ πÿπ°“√„™â epoetin ‚¥¬‡©æ“–™π‘¥ short- acting ∑’˧«“¡∂’ËπâÕ¬°«à“ 1 §√—ÈßµàÕ —ª¥“Àå „π EBPG ·π–𔧫“¡∂’Ë„π°“√„À⬓¢÷Èπ°—∫¢π“¥, route, treatment phase, ™π‘¥¢Õß ESA, ™π‘¥¢Õß dialysis „πºŸâªÉ«¬øÕ°‡≈◊Õ¥ ∂â“„Àâ epoetin-alpha À√◊Õ beta ∑“ß IV §«√„Àâ 3 §√—ÈßµàÕ —ª¥“Àå ·µà∂â“„Àâ epoetin-β sc Õ“®„À⇪ìπ 1-2 §√—ÈßµàÕ —ª¥“Àå  à«π„πºŸâªÉ«¬≈â“ß ‰µ∑“ß™àÕß∑âÕß epoetin-β „Àâ 3 §√—ÈßµàÕ —ª¥“Àå„π™à«ß correction ·≈–≈¥‡ªìπ 1 §√—ÈßµàÕ —ª¥“Àå „π™à«ß maintenance  à«π darbepoetin-α „π™à«ß correction „Àâ 1 §√—ÈßµàÕ —ª¥“Àå IV À√◊Õ sc „πºŸâªÉ«¬øÕ°‡≈◊Õ¥ ·≈– 1 §√—ÈßµàÕ —ª¥“Àå sc „πºâŸªÉ«¬≈â“߉µ∑“ß™àÕß∑âÕß  à«π„π™à«ß maintenance Õ“®„Àâ∑ÿ° 2-4  —ª¥“Àå „πºªŸâ «É ¬∑‡’Ë §¬‰¥â epoetin-α, epoetin-β 1 §√ß—È µÕà  ª— ¥“Àå  “¡“√∂‡ª≈¬’Ë π¡“„Àâ darbepoetin-α ∑°ÿ 2  ª— ¥“Àå ‰¥â33  ”À√—∫ DOQI ·π–π”„Àâæ‘®“√≥“§«“¡∂’Ë„π°“√„À⬓ ®“°√–¬–¢Õ߉µ«“¬‡√◊ÈÕ√—ß, treatment setting, efficacy ·≈–™π‘¥¢Õß ESA ´÷Ëß∂Ⓡªìπ short acting °“√ extend interval Õ“®¡’º≈≈¥ª√– ‘∑∏‘¿“æ ¢Õ߬“29 5.6 °“√ª√∫— ¢π“¥¢Õ߬“ ESA DOQI ‰¥â·π–π”„Àâæ‘®“√≥“¢π“¥¬“‡√‘Ë¡µâπ·≈–ª√—∫µ“¡√–¥—∫ Hb ‡√‘Ë¡·√°¢Õߺ⟪ɫ¬·≈– 175

Practical Dialysis in the Year 2009 Õ—µ√“°“√‡æ‘Ë¡¢Õß Hb ‚¥¬§«√¡’°“√µ‘¥µ“¡ Hb Õ¬à“ßπâÕ¬∑ÿ°‡¥◊Õπ ·≈–§«√„ÀâÕ—µ√“°“√‡æ‘Ë¡¢Õß Hb 1-2 g/dL µàÕ‡¥◊Õπ ‡æ◊ËÕ≈¥‚Õ°“ ‡°‘¥º≈¢â“߇§’¬ß„π·ß৫“¡¥—π‚≈À‘µ ßŸ À√◊Õ™—° §«“¡∂’Ë„π°“√ª√—∫¬“¢÷Èπ°—∫ Õ—µ√“°“√‡æ‘Ë¡¢÷Èπ, §«“¡§ß∑’Ë¢Õß Hb „π™à«ß maintenance ·≈–§«“¡∂’Ë„π°“√µ√«® Hb ·µà‰¡à§«√ª√—∫¬“ ∂’Ë°«à“∑ÿ° 2  —ª¥“Àå ·≈–„π°√≥’∑’Ë Hb  ßŸ °«à“ target, ‡¢â“√—∫°“√√—°…“„π‚√ß欓∫“≈, §«“¡¥—π‚≈À‘µ ßŸ §«∫§ÿ¡‰¥â‰¡à¥’ À√◊Õ¡’ vascular access occlusion ‰¡à§«√À¬ÿ¥¬“·µà§«√„ÀâµàÕ‰ª ·µà§«√≈¥¢π“¥¬“≈ß29 Õ’°ªí®®—¬∑’˧«√§”π÷ß∂÷ß„π°“√ª√—∫¬“ ESA §◊Õ fluctuation ¢Õß§à“ Hb ´÷Ëß¡’√“¬ß“π«à“æ∫∂÷ß √âÕ¬≈– 90 ¢Õߺ⟪ɫ¬øÕ°‡≈◊Õ¥∑’Ë¡’Õ¬à“ßπâÕ¬ 1 §√—Èß ∑’Ë§à“ Hb excursion ¡“°°«à“ 1.5 g/dL ‡ªìπ‡«≈“π“π Õ¬à“ßπâÕ¬ 8  —ª¥“ÀåµàÕªï ·≈–¡’°“√·°«àߢÕß Hb ‡©≈’ˬ 3.8 √Õ∫µàÕªï ·≈–¡’ Hb excursion 2.5 g/dL ¥—ß π—Èπ∂⓵—Èß target Hb ‰«â∑’Ë 12 g/dL °Á¡’‚Õ°“ ∑’Ë Hb ®–¡“°°«à“ 12 g/dL ‰¥â7 ´÷Ëß®“°¢âÕ¡≈Ÿ ∑’Ë¡’√“¬ß“π°Áæ∫ «à“ Hb ∑’ˠߟ ∑”„À⇰‘¥º≈‡ ’¬„πºâŸªÉ«¬ dialysis  “‡Àµÿ∑’Ë∑”„À⇰‘¥°“√·°«àߢÕß Hb ¬—߉¡à√⟷πàπÕ𠧑¥«à“‡°‘¥®“°À≈“¬ªí®®—¬√à«¡°—π ªí®®—¬ ∑’Ë∑”„Àâ¡’°“√·°«àߢÕß Hb „πºŸâªÉ«¬ dialysis Õ“®‡°‘¥®“°°“√ª√—∫¢π“¥¢Õß ESA ∫àÕ¬‡°‘π‰ª, °“√¡’ iron store ∑‰’Ë ¡‡à 欒 ßæÕ, °“√‡ª≈¬’Ë π·ª≈ߢÕß fluid balance, §«“¡‡®∫Á ª«É ¬À√Õ◊ ‡¢“â √∫— °“√√°— …“„π‚√ß欓∫“≈, intrinsic patient variability °“√„™â short-acting ESA Õ“®∑”„Àâ¡’°“√·°«àߢÕß Hb ∑”„ÀâµâÕß¡’°“√µ‘¥µ“¡·≈–ª√—∫¢π“¥ ¢Õ߬“∫àÕ¬¢÷Èπ ∑—Èßπ’ÈÕ“®‡ªìπº≈®“°°“√ª√—∫‡æ‘Ë¡¢π“¥¢Õ߬“‡√Á«‡°‘π‰ª°«à“°”À𥇫≈“∑’ˬ“®–ÕÕ° ƒ∑∏‘χæ‘Ë¡ Hb ∑”„À⺟âªÉ«¬‰¥â√—∫¢π“¥¢Õ߬“ ßŸ ‡¡◊ËÕ¬“ÕÕ°ƒ∑∏‘χµÁ¡∑’Ë §à“ Hb ®÷ß Ÿß°«à“ target ∑’˵âÕß°“√ ¡’°“√»÷°…“æ∫«à“ ‡æ’¬ß√âÕ¬≈– 40 ¢Õߺ⟪ɫ¬ dialysis ∑’Ë¡’§à“ Hb Õ¬Ÿà„π™à«ß 11-12 g/dL ≥ ‡«≈“Àπ÷Ëß Õ’°√“¬ß“πæ∫«à“¡’‡æ’¬ß√âÕ¬≈– 5 ¢ÕߺŸâªÉ«¬øÕ°‡≈◊Õ¥∑’Ë¡’§à“ Hb §ß∑’Ë ∑’Ë√–¥—∫ 11-12 g/dL ‡ªì𠇫≈“π“π 6 ‡¥◊Õπ ·≈–®“° USRDS æ∫«à“√âÕ¬≈– 97 ¢Õߺ⟪ɫ¬ dialysis ¡’ Hb ¡“°°«à“ 12 g/dL ·≈–√âÕ¬ ≈– 42 ¡’ Hb ¡“°°«à“ 14 g/dL ¿“¬„π 6 ‡¥◊ÕπÀ≈—ß®“°‰¥â target Hb 11 g/dL ‚¥¬„πºâŸªÉ«¬≈â“߉µ∑“ß™àÕß ∑âÕß¡’‚Õ°“ ∑’Ë Hb ®–¡“°°«à“ 12 g/dL πâÕ¬°«à“ºŸâªÉ«¬øÕ°‡≈◊Õ¥1 ªí≠À“ overshooting ¢Õß Hb æ∫‰¥â¡“° ·≈–°“√¡’ fluctuation ¢Õß Hb ¡“°π’È ¡’§«“¡  —¡æ—π∏å°—∫ poor outcome ®“°°“√»÷°…“ºâŸªÉ«¬øÕ°‡≈◊Õ¥®”π«π 152,846 √“¬ ∑’ˉ¥â√—∫ ESA æ∫«à“ºâŸªÉ«¬ ∑ ’Ë “¡“√∂ maintain Hb „À§â ß∑„’Ë π™«à ß target 11-12.5 g/dL ‰¥â ®–¡Õ’ µ— √“°“√‡¢“â √∫— °“√√°— …“„π‚√ß欓∫“≈ ‚¥¬‡©æ“–®“° “‡Àµÿ°“√µ‘¥‡™◊Èյ˔∑’Ë ÿ¥ ·≈–√–¬–‡«≈“°“√‡¢â“√—∫°“√√—°…“„π‚√ß欓∫“≈ —Èπ∑’Ë ÿ¥41 °“√„™â¬“ ESA ∑’Ë long-acting ´÷Ëß¡’°“√°√–µÿâπ°“√ √â“߇¡Á¥‡≈◊Õ¥·¥ß∑’˧ß∑’Ë„π√–¬–‡«≈“¬“« Õ“®∑”„À≥Ⱃ√µÕ∫ πÕß∑’˧ß∑’Ë ¡’°“√·°«àߢÕß Hb µË”°«à“28 ®“°°“√»÷°…“‚¥¬ Berns JS ·≈–§≥– „πºŸâªÉ«¬øÕ°‡≈◊Õ¥ 987 √“¬ ∑’ˉ¥â√—∫°“√√—°…“¥â«¬ epoetin æ∫«à“ range of Hb ∑’Ë encompass √âÕ¬≈– 90 ¢Õߺ⟪ɫ¬ ‡∑à“°—∫ 4.4 g/dL ∂â“«—¥ Hb ∑ÿ° 1 ‡¥◊Õπ §à“π’È®–‡ªìπ 3.7 g/dL ∂â“„™â§à“‡©≈’ˬ 3 ‡¥◊Õπ ·≈–‡ªìπ 3.2 g/dL ∂â“„™â§à“ Hb ‡©≈’ˬ 6 ‡¥◊Õπ ¥—ßπ—Èπ®“°°“√ »÷°…“π’È®÷ß·π–π”«à“ ∂â“„™â§à“‡©≈’ˬ∑’Ë 3-6 ‡¥◊Õπ„π°“√ª√–‡¡‘π°“√√—°…“Õ“®¥’°«à“ °“√„™â§à“∑ÿ° 1 ‡¥◊Õπ ‡π◊ËÕß®“°¡’°“√·°«àßπâÕ¬°«à“42 ·µàÕ¬à“߉√°Áµ“¡ ®“°·π«∑“ß°“√ªØ‘∫—µ‘∑’Ë¡’°“√·π–π”·≈–π‘¬¡„™â ¬—ß ·π–π”„Àâµ√«®‡≈◊Õ¥¥Ÿ√–¥—∫ Hb ∑ÿ°‡¥◊Õπ ·≈–π”¡“æ‘®“√≥“„π°“√ª√—∫¬“ 176

Current Management of Anemia in Dialysis Patients 5.7 º≈¢“â ߇§’¬ß¢Õß ESA ¥—ßµ“√“ß∑’Ë 2 µ“√“ß∑’Ë 2 · ¥ßº≈¢â“߇§’¬ß¢Õß°“√„™â ESA „πºŸâªÉ«¬≈â“߉µ 1. §«“¡¥—π‚≈À‘µ ßŸ 2. Õ“°“√™—° 3. hemodialysis vascular access clotting 4. dialysis efficacy and dialyzer clotting 5. influenza-like symptom º≈¢â“߇§’¬ß¢Õß°“√„™â ESA ‰¥â·°à 5.7.1 §«“¡¥—π‚≈À‘µ Ÿß43,44 æ∫«à“ ESA  “¡“√∂∑”„À⧫“¡¥—π‚≈À‘µ ßŸ ¢÷Èπ‰¥â æ∫„π√âÕ¬≈– 30-40 ¢ÕߺŸâªÉ«¬ ‚¥¬Õ“® ‡ªìπºâŸªÉ«¬∑’ˉ¡à‡§¬¡’§«“¡¥—π‚≈À‘µ Ÿß¡“°àÕπ À√◊Õ¡’‚√§ª√–®”µ—«‡ªìπ‚√§§«“¡¥—π‚≈À‘µ Ÿß‡¥‘¡ ªí®®—¬∑’Ë —¡æ—π∏å°—∫°“√‡æ‘Ë¡¢÷Èπ¢Õߧ«“¡¥—π‚≈À‘µ∑’Ë —¡æ—π∏å°—∫°“√„™â ESA 5.7.1.1 °“√¡’§«“¡¥—π‚≈À‘µ Ÿß¡“°àÕπ 5.7.1.2 ´’¥¡“°‡¡◊ËÕ‡√‘Ë¡„À⬓ 5.7.1.3 Hb ‡æ‘Ë¡¢÷ÈπÕ¬à“ß√«¥‡√Á« ®“°¢âÕ¡≈Ÿ ¢Õß Canadian Multicenter Epo Study æ∫«à“¡’ §«“¡ —¡æ—π∏åÕ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘µ‘ √–À«à“ß°“√‡ª≈’ˬπ·ª≈ߢÕß Hb °—∫§«“¡¥—π‰¥·Õ ‚µ≈‘° „π 5  —ª¥“Àå·√°¢Õß°“√„À⬓ (r= 0.42, p< 0.001) 5.7.1.4 ¡’°“√„™â¬“„π¢π“¥∑’Ë Ÿß∑“ß IV ¢π“¥¢Õß epoetin ∑’Ë¡“°°«à“ 200 IU/kg ∑’Ë„Àâ 3 §√—Èß µàÕ —ª¥“Àå ¡’§«“¡ —¡æ—π∏å°—∫°“√‡°‘¥º≈¢â“߇§’¬ß∑’Ë√ÿπ·√ß ‡™à𧫓¡¥—π‚≈À‘µ Ÿß, hypertensive encephalopathy, ™—° ·≈–æ∫«à“°“√‡√‘Ë¡„Àâ epoetin ¢π“¥ 50 IU/kg 3 §√—ÈßµàÕ —ª¥“Àå  “¡“√∂ correct ¿“«–´¥’ ‰¥¡â “°°«“à √Õâ ¬≈– 90 „π 8-12  ª— ¥“Àå ¥ß— ππÈ— §«√‡√¡Ë‘ ¥«â ¬¢π“¥∑µË’ ”Ë °Õà π·≈«â §Õà ¬ª√∫— ¢π“¥µ“¡ °“√µÕ∫ πÕß2 5.7.1.5 °“√¡’‰µ‡°à“¢Õߺ⟪ɫ¬ °≈‰°∑Ë’∑”„À⧫“¡¥—π‚≈À‘µ Ÿß¢÷πÈ À≈ß— ‰¥â¬“ ESA43 1. loss of hypoxic vasodilatation °“√»÷°…“‚¥¬ Roger ·≈–§≥– æ∫«à“ total peripheral resistance ∑’Ë forearm ‡æ‘Ë¡¢÷Èπ‡¡◊ËÕ¡’ oxygen delivery ¡“°¢÷Èπ Õ“®‚¥¬°“√¡’ supplemental oxygen À√◊Õ Hct ¡“°¢÷Èπ ´÷Ëß total peripheral resistance ∑’ˇæ‘Ë¡¢÷Èπ ∑”„À⧫“¡¥—π‚≈À‘µ ßŸ ¢÷Èπ 2. blood viscosity ‡æ‘Ë¡¢÷Èπ 3. ¡’°“√‡æ‘Ë¡¢Õߪ√‘¡“≥‡≈◊Õ¥„π√à“ß°“¬ 177

Practical Dialysis in the Year 2009 4. ¡’°“√°√–µÿâπ renin angiotensin system 5. ¡’√–¥—∫ endothelin ‡æ‘Ë¡¢÷Èπ ·≈–√–¥—∫ nitric oxide ≈¥≈ß ∑”„À⧫“¡¥—π‚≈À‘µ Ÿß¢÷Èπ 6. ¡’°“√‡æ‘Ë¡¢Õß vascular calcium uptake ®“°°“√»÷°…“‚¥¬ Neusser ·≈–§≥– æ∫«à“ epo ¡’º≈‡æ‘Ë¡ vascular smooth muscle cell free calcium in vitro ‰¥â 7. platelet-dependent mitogenic action Caravaca ·≈–§≥– æ∫«“à °“√‡°¥‘ §«“¡¥π— ‚≈Àµ‘  ßŸ æ∫„π§π∑‰’Ë ¥√â ∫— antiplatelet therapy πÕâ ¬ °«à“§π∑’ˉ¡à‰¥â√—∫ ‚¥¬∑’ˬ—߉¡à√⟰≈‰° ·≈–¡’Õ’°°“√»÷°…“ æ∫«à“ªí®®—¬∑’Ë∑”𓬰“√‡°‘¥§«“¡¥—π‚≈À‘µ ßŸ ∑’Ë¥’∑’Ë ÿ¥ §◊Õ °“√„™â antiplatelet (OR 0.03, p< 0.0001), Õ“¬ÿ ·≈– preexistin hypertension2 ¥—ßπ—Èπ§«√¡’°“√§—¥‡≈◊Õ°ºâŸªÉ«¬∑’ˇÀ¡“– ¡„π°“√„À⬓ ∂â“¡’§«“¡¥—π‚≈À‘µ ŸßÕ¬Ÿà‡¥‘¡ §«√ §«∫§ÿ¡°àÕπ„À⬓57 ·≈–§«√¡’°“√µ‘¥µ“¡§«“¡¥—π‚≈À‘µÕ¬à“ß ¡Ë”‡ ¡ÕÀ≈—ß®“°‡√‘Ë¡ ∂ⓧ«“¡¥—π‚≈À‘µ  ßŸ ¢÷È𠧫√ª√—∫¬“≈¥§«“¡¥—π‚≈À‘µ À√◊Õ≈¥¢π“¥¬“ ESA ≈ß ·µà‰¡à®”‡ªìπµâÕßÀ¬ÿ¥„Àâ ¬°‡«âπ„π°√≥’∑’Ë §«“¡¥—π‚≈À‘µ ßŸ ¡“°®π§«∫§ÿ¡‰¡à‰¥1â 3 5.7.2 Õ“°“√™—° ¡’√“¬ß“π æ∫ grand mal seizure 6 „π 68 √“¬ ‚¥¬ 3 √“¬‡°‘¥„π 3 ‡¥◊Õπ·√°¢Õß°“√„À⬓ ´÷Ëß Hb ·≈–§«“¡¥—π‚≈À‘µ ßŸ ¢÷Èπ‡√Á«„π™à«ß‡«≈“π—Èπ Õ“® —¡æ—π∏å°—∫°“√∑’Ë¡’ red cell mass ‡æ‘Ë¡¢÷È𠧫“¡ ¥—π‚≈À‘µ Ÿß¢÷Èπ ·≈–≈¥ seizure threshold9 ®“° Canadian multicenter trial ‰¡àæ∫«à“ºâŸªÉ«¬∑’ˉ¥â ESA ¡’§«“¡‡ ’ˬ߄π°“√‡°‘¥Õ“°“√™—° ¡“°¢÷Èπ Õ“®‡π◊ËÕß®“°„π°“√»÷°…“π’È ¡’°“√§«∫§ÿ¡§«“¡¥—π‚≈À‘µ‰¥â¥’ ¡’√“¬ß“πæ∫«à“§«“¡‡ ’ˬß∑’Ë®–¡’Õ“°“√™—° Ÿß¢÷Èπ„πºâŸªÉ«¬∑’Ë´’¥¡“°°àÕπ‡√‘Ë¡„À⬓ ·µà¬—߉¡à√⟠°≈‰° ·µàÕ¬à“߉√°Áµ“¡ ‰¡à¡’¢âÕ¡Ÿ≈«à“ ESA  “¡“√∂∑”„À⇰‘¥Õ“°“√™—°‰¥â‚¥¬µ√ß2 5.7.3 Hemodialysis vascular access clotting ¡’√“¬ß“π√âÕ¬≈– 26 ¢Õߺ⟪ɫ¬∑’ˉ¥â√—∫ ESA ¡’ªí≠À“ access failure ‚¥¬ à«π¡“°‡ªìπ polytetrafluoroethylene graft √“¬ß“π®“°¬ÿ‚√ª æ∫ graft clotting √âÕ¬≈– 14.7 °≈‰°°“√‡°‘¥ vascular access clotting ‰¥â·°à °“√‡æ‘Ë¡¢Õß Hct, red blood cell-platelet, red blood cell-endothelium interaction, endothelial-derived FVIII-vWF Ag, plasma fibrinogen, ¡’°“√≈¥≈ߢÕß protein C, protein S ·≈–¡’°“√‡æ‘Ë¡ ¢Õß platelet aggregation ¥—ßπ—Èπ„πºŸâªÉ«¬∑’ˉ¥â√—∫ ESA §«√¡’°“√ª√–‡¡‘𵑥µ“¡ vascular access Õ¬à“ß  ¡Ë”‡ ¡Õ¥â«¬ 5.7.4 Dialysis efficacy and dialyzer clotting „π°“√»÷°…“√–¬–·√° ¡’√“¬ß“π«à“µâÕ߇æ‘Ë¡¢π“¥¢Õß heparin ¡“°¢÷Èπ„π√–À«à“ß°“√øÕ° ‡≈Õ◊ ¥ ·µ‰à ¡æà ∫º≈¥ß— °≈“à «„π°“√»°÷ …“√–¬–µÕà ¡“ ·≈–‰¡æà ∫«“à ESA ¡º’ ≈µÕà dialyzer performance À√Õ◊ µâÕߪ√—∫ dialysis prescription 178

Current Management of Anemia in Dialysis Patients 5.7.5 influenza-like symptom ¡√’ “¬ß“πæ∫Õ“°“√ª«¥‡¡Õ◊Ë ¬°≈“â ¡‡πÕ◊È , ª«¥»√’ …–, flank pain, µ“·¥ß „π uncontrolled study ·µà‰¡àæ∫√“¬ß“π„π controlled study2  «à πº≈¢“â ߇§¬’ ߢÕß darbepoetin-α ∑¡Ë’ √’ “¬ß“π„π°“√»°÷ …“‰¥·â °à §«“¡¥π— ‚≈Àµ‘  ßŸ æ∫√Õâ ¬ ≈– 18, §«“¡¥π— ‚≈Àµ‘ µ”Ë æ∫√Õâ ¬≈– 22, ª«¥°≈“â ¡‡πÕÈ◊ , ª«¥»√’ …–, Õ®ÿ ®“√–√«à ß, °“√µ¥‘ ‡™ÕÈ◊  «à πÕ“°“√ ª«¥∑’˵”·Àπàß©’¥¬“ æ∫√âÕ¬≈– 57,45 º≈¢â“߇§’¬ß¢Õß CERA ®“°°“√»÷°…“ ‰¥â·°à §«“¡¥—π‚≈À‘µ Ÿß, postural hypotension, ª«¥ »’√…–, Õÿ®®“√–√à«ß ·≈– nasopharyngitis º≈¢â“߇§’¬ß∑’Ë —¡æ—π∏å°—∫°“√„À⬓ æ∫√âÕ¬≈– 4 „π°“√„À⬓ ∑ÿ° 2 ‡¥◊Õπ ·≈–√âÕ¬≈– 6 „π°“√„À⬓∑ÿ°‡¥◊Õπ ¡’ 3 √“¬∑’Ëæ∫Õ“°“√™—°, AVF thrombosis, GI necrosis ·≈– sepsis40 6. °“√„™â Adjuvant „πºâŸª«É ¬∑’‰Ë ¥√â —∫ ESA ®“°¢âÕ¡Ÿ≈¢Õß USRDS »÷°…“„πºŸâªÉ«¬øÕ°‡≈◊Õ¥®”π«π 94,569 √“¬ „π™à«ßªï 2000-2001 æ∫«à“¡’§«“¡·µ°µà“ß√–À«à“ß¢π“¥¢Õß epoetin ∑’˺⟪ɫ¬µâÕß„™â„π°“√„À≥â Hct ∑’˵âÕß°“√ ·≈–¬—ßæ∫ «à“ºŸâªÉ«¬∑’˵âÕß„™â¢π“¥¢Õß epoetin  ßŸ ®–¡’§à“ Hct µË”°«à“ ·≈–¡’Õ—µ√“°“√‡ ’¬™’«‘µ Ÿß°«à“ºâŸªÉ«¬∑’Ë„™â¬“ ¢π“¥µË”°«à“Õ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘µ‘ · ¥ß«à“¢π“¥¢Õß epoetin ∑’Ë„™â ‡ªìπ independent predictor ¢Õß Õ—µ√“°“√‡ ’¬™’«‘µ¢ÕߺŸâªÉ«¬øÕ°‡≈◊Õ¥ „πºâŸªÉ«¬∑’˵Õ∫ πÕ߉¡à¥’ ®–¬—ߧߡ’ Hct ∑’˵˔ ·¡â«à“®–‡æ‘Ë¡¢π“¥ ¢÷Èπ‰ª°Á‰¡à‰¥âª√–‚¬™πå‡æ‘Ë¡¢÷Èπ ¥—ßπ—Èπ„πºâŸªÉ«¬°≈ÿà¡π’È Õ“®æ‘®“√≥“°“√„Àâ adjuvant therapy46 Adjuvant therapy ‡ªπì °“√√°— …“∑Õ’Ë “®™«à ¬„À°â “√µÕ∫ πÕßµÕà ESA ¥¢’ π÷È ‚¥¬‰¡µà Õâ ß‡æ¡‘Ë ¢π“¥ ¬“ ESA À√◊Õ “¡“√∂≈¥¢π“¥¢Õß ESA ∑’Ë„™â‰¥â ‚¥¬‰¡à¡’°“√‡ª≈’ˬπ·ª≈ߢÕß Hb ·≈–¬—ßÕ“®™à«¬≈¥ §«“¡®”‡ªìπ„π°“√„Àâ‡≈◊Õ¥·°àºâŸªÉ«¬ 47 Adjuvant ∑’Ë¡’„™â ‰¥â·°à 1. «‘µ“¡‘π ´’ À√Õ◊ ascorbic acid „πºâŸªÉ«¬∑’ˉ¥â√—∫°“√√—°…“¥â«¬ dialysis Õ“®¡’°“√¢“¥«‘µ“¡‘π´’ ´÷Ëß°“√¢“¥π’ÈÕ“®∑”„À⇰‘¥ oxidative stress, vascular complication, °“√¥Ÿ¥´÷¡‡À≈Á°∑’Ë≈”‰ â‡ ’¬‰ª ·≈–°“√ mobilize ‡À≈Á°ÕÕ°®“° iron store ‡°‘¥¢÷Èπ‰¥â‰¡à¥’ «µ‘ “¡π‘ ´Õ’ “®∑”„À°â “√ √“â ߇¡¥Á ‡≈Õ◊ ¥·¥ß¥¢’ ÷πÈ ‚¥¬º≈ antioxidant ·≈–¬ß— æ∫«“à ‡¡ÕË◊ π”¡“„Àâ ∑“߇ πâ ‡≈Õ◊ ¥  “¡“√∂‡æ¡‘Ë iron release ÕÕ°®“° reticuloendothelial system ·≈– ferritin ∑”„À§â “à transferrin saturation (TSAT) ¥’¢÷Èπ ·≈–≈¥ soluble transferrin receptor ‡æ‘Ë¡°“√„™â‡À≈Á°„π°“√ √â“ß heme 41,48,49 ®“°°“√»÷°…“„πºŸâªÉ«¬øÕ°‡≈◊Õ¥∑’ˉ¥â√—∫ IV iron sucrose æ∫«à“°“√„Àâ ascorbic acid IV 500 mg 3 §√—ÈßµàÕ —ª¥“Àå ‡ªìπ‡«≈“ 6 ‡¥◊Õπ  “¡“√∂‡æ‘Ë¡ TSAT ·≈– Hb ‰¥â√âÕ¬≈–15 ¢Õߺ⟪ɫ¬ Õ¬à“߉√ °Áµ“¡°“√»÷°…“º≈¢Õß«‘µ“¡‘π´’ IV „πºŸâªÉ«¬øÕ°‡≈◊Õ¥ ¡—°∑”„ÀâºâŸªÉ«¬∑’Ë¡’ iron overload ·≈– functional 179

Practical Dialysis in the Year 2009 iron deficiency ·µàº≈°“√»÷°…“‰¡à·πàπÕπ 49 ·≈–°“√„Àâ«‘µ“¡‘π´’ IV Õ“®∑”„À⇰‘¥ systemic oxalosis ∂â“√–¥—∫ oxalate „π‡≈◊Õ¥¡“°°«à“ 50-100 µmol/L50 ∂â“„À⧫√¡’°“√µ‘¥µ“¡√–¥—∫¢Õß oxalate „π‡≈◊Õ¥ „π DOQI ·π–π”«à“‰¡à¡’À≈—°∞“π‡æ’¬ßæÕ∑’Ë®–„Àâ«‘µ“¡‘π´’„πºâŸªÉ«¬‰µ«“¬‡√◊ÈÕ√—߇æ◊ËÕ√—°…“¿“«–´’¥ ·µà„π EBPG °“√„Àâ«‘µ“¡‘π´’„π§π∑’Ë¢“¥  “¡“√∂≈¥ resistance to ESA ‰¥â ·µà∂â“„Àâ IV „π¢π“¥ ßŸ §«√¡’°“√ µ‘¥µ“¡33  ”À√—∫°“√°‘π«‘µ“¡‘π´’‰¡à¡’º≈µàÕ oxidative/antioxidative stress ·≈– inflammatory marker „πºªŸâ «É ¬øÕ°‡≈Õ◊ ¥·≈–¡°’ “√»°÷ …“æ∫«“à °“√°π‘ «µ‘ “¡π‘ ´‰’ ¡¡à º’ ≈µÕà √–¥∫— Hb ·≈–¢π“¥¢Õß ESA πÕ°®“° π’È°“√„Àâ°‘π«‘µ“¡‘π´’„π¢π“¥∑’ˠߟ ¬—ßÕ“®¡’º≈‡ ’¬§◊Õ°“√¥Ÿ¥´÷¡Õ≈¡Ÿ ‘‡π’¬¡∑’Ë≈”‰ â‡æ‘Ë¡¢÷Èπ¥â«¬45 2. Androgen „πÕ¥’µ°“√√—°…“¿“«–´’¥„πºâŸªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß„™â androgen ‡ªìπ°“√√—°…“À≈—° ¡’°“√»÷°…“ „πºâŸªÉ«¬øÕ°‡≈◊Õ¥ æ∫«à“°“√µÕ∫ πÕßµàÕ nandrolone decanoate ¢÷Èπ°—∫Õ“¬ÿ ‚¥¬„πºâŸ™“¬ Õ“¬ÿ¡“° ®– µÕ∫ πÕ߉¥â¥’°«à“ºâŸªÉ«¬°≈ÿà¡Õ◊Ëπ ‚¥¬°“√µÕ∫ πÕßÕ“®¥’‡À¡◊Õπ°—∫°“√√—°…“¥â«¬ epoetin πÕ°®“°π’È „πºâŸªÉ«¬≈â“߉µ∑“ß™àÕß∑âÕß ¡’√“¬ß“π«à“ androgen ™à«¬∑”„Àâ Hb ·≈– Õ—≈∫¡Ÿ ‘π„π‡≈◊Õ¥¥’¢÷Èπ °“√»÷°…“‚¥¬ Navaro JF ·≈–§≥– „πºâŸªÉ«¬™“¬∑’ˉ¥â√—∫°“√≈â“߉µ∑“ß™àÕß∑âÕß ∑’ËÕ“¬ÿ¡“° °«à“ 50 ªï ®”π«π 27 √“¬ ‡ª√’¬∫‡∑’¬∫√–À«à“ß°“√‰¥â√—∫ epoetin °—∫ nandrolone decanoate 200 mg ©’¥ ‡¢â“°≈â“¡‡π◊ÈÕ ∑ÿ° —ª¥“Àå ‡ªìπ‡«≈“ 6 ‡¥◊Õπ æ∫«à“°≈ÿà¡∑’ˉ¥â epoetin ¡’ Hb ‡æ‘Ë¡¢÷Èπ‡©≈’ˬ 3.1±0.9 g/dL, serum albumin ‡æ‘Ë¡¢÷Èπ√âÕ¬≈– 36±10 ·≈–„π°≈ÿà¡∑’ˉ¥â√—∫ androgen ¡’ Hb ‡æ‘Ë¡¢÷Èπ‡©≈’ˬ 2.9±0.7 g/dL, serum albumin ‡æ‘Ë¡¢÷Èπ√âÕ¬≈– 21±10 ‚¥¬„π°≈ÿà¡∑’ˉ¥â androgen §«“¡¥—π‚≈À‘µ‡æ‘Ë¡¢÷Èπ√âÕ¬≈– 6 ‰¡à¡’ °“√‡ª≈’ˬπ·ª≈ߢÕß°“√∑”ß“πµ—∫ ¡’ triglyceride ‡æ‘Ë¡¢÷Èπ ·≈– HDL ≈¥≈ß ·µà‡≈Á°πâÕ¬·≈–‡ªìπ‡æ’¬ß ™—Ë«§√“«51 °≈‰°∑’Ë androgen ™«à ¬‡æË¡‘ °“√ √“â ߇¡¥Á ‡≈◊Õ¥·¥ß¬ß— ‰¡à™¥— ‡®π Õ“®¡’º≈°√–µπâÿ °“√ √â“ß epo ®“°‰µÀ√◊ÕÕ«—¬«–∑’ˉ¡à„™à‰µ À√◊Õ‡æ‘Ë¡§«“¡‰«¢Õß erythroid progenitor µàÕ epo À√◊ÕÕ“®¡’º≈‚¥¬µ√ßµàÕ erythropoietic precursor À√◊Õ‡æ‘Ë¡ red blood cell survival ®“°°“√»÷°…“°“√„™â nandrolone decanoate „π ºªâŸ «É ¬≈“â ߉µ∑“ß™Õà ß∑Õâ ß æ∫«“à ¡√’ –¥∫— IGF-1 ‡æ¡Ë‘ ¢πÈ÷ ¥«â ¬ ´÷ßË IGF-1 π¡È’ º’ ≈‡æ¡Ë‘ erythroid colony formation, maturation ·≈– proliferation51 °“√»÷°…“Õ◊Ëπ∑’Ë¡’√“¬ß“π¡—°‡ªìπ°“√»÷°…“¢π“¥‡≈Á° ¡’°“√µ‘¥µ“¡ºâŸªÉ«¬‰¡àπ“π ·≈–‰¡à‡ªìπ ºâŸªÉ«¬∑’Ë¡’ªí≠À“ hyporesponsiveness to ESA ∑”„À≡à∑√“∫ª√– ‘∑∏‘¿“æ¢Õß androgen „πºâŸªÉ«¬°≈ÿà¡π’È Õ°’ ∑ßÈ— º≈¢“â ߇§¬’ ß∑æË’ ∫‰¥â ‰¥·â °à  «‘ , virilizatiion, priapism, °“√∑”ß“π¢Õßµ∫— º¥‘ ª°µ,‘ Õ“°“√ ª«¥∑’˵”·Àπàß©’¥¬“ ·≈–§«“¡‡ ’ˬߵàÕ°“√‡°‘¥ peliosis hepatis ·≈– hepatocellular carcinoma ‡π◊ËÕß®“°ª√– ‘∑∏‘¿“æ¢Õß androgen ¬—߉¡à™—¥‡®π ·≈–¡’º≈¢â“߇§’¬ß∑’˧àÕπ¢â“ß√ÿπ·√ß ¡’¢âÕ ®”°—¥„π°“√„™â„πºŸâªÉ«¬À≠‘ß ¥—ßπ—Èπ„π DOQI ‰¥â·π–π”«à“‰¡à§«√„™â‡ªìπ adjuvant „πºŸâªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß ·µà„π EBPG Õ“®æ‘®“√≥“„™â„πºâŸªÉ«¬∫“ß√“¬ ‰¥â·°à ºŸâ™“¬ Õ“¬ÿ¡“°°«à“ 50 ªï ‰¥â√—∫°“√≈â“߉µ∑“ß™àÕß ∑âÕß °“√„Àâ nandrolone decanoate 200 mgµàÕ —ª¥“Àå Õ“®≈¥Õ“°“√®“°¿“«–´’¥ ·≈–¡’ª√–‚¬™πå„π °“√ improve ¿“«–‚¿™π“°“√33 180

Current Management of Anemia in Dialysis Patients 3. L-carnitine L-carnitine ‡ªìπ carrier molecule ¡’∫∑∫“∑„π°“√¢π àß long-chain fatty acid ‡¢â“‰ª„π mitochondria µàÕ¡“¡’°“√ oxidation ‡æ◊ËÕ √â“ßæ≈—ßß“π ·≈– L-carnitine ¬—ßÕ“®¡’∫∑∫“∑„π°“√‡ª≈’ˬπ acyl Coenzyme A ‡ªìπ acyl carnitine ´÷Ë߇ªìπæ‘…µàÕ‡´≈≈åπâÕ¬°«à“ Õ“®¡ª’ √–‚¬™π„å π ESA-hyporesponsive anemia, hemodialysis-related hypotension, myocardial dysfunction, impaired exercise tolerance, muscle symptom ·≈– impaired nutritional status ¡’ systematic review ∑’Ëæ∫«à“ L-carnitine ¡’ª√–‚¬™πå„πºâŸªÉ«¬∑’ˉ¥â√—∫ ESA ·µà¡’ªí≠À“ trial heterogeneity50 DOQI  √ÿª«à“‰¡à¡’¢âÕ¡≈Ÿ ‡æ’¬ßæÕ„π°“√„™â L-carnitine „π°“√¥·Ÿ ≈ªí≠À“´’¥„πºâŸªÉ«¬‰µ«“¬ ‡√◊ÈÕ√—ß49 ·µà®“° systematic review ·≈–°“√»÷°…“„πºŸâªÉ«¬øÕ°‡≈◊Õ¥ ∑’Ëæ∫«à“Õ“®¡’ª√–‚¬™πå„π°“√ improve Hb ·≈–Õ“®≈¥¢π“¥¢Õß ESA ‰¥â„πºâŸªÉ«¬∑’ˉ¡àµÕ∫ πÕßµàÕ ESA ∑”„Àâ EBPG ·π–π”°“√„™â L-carnitine Õ“®¡’ª√–‚¬™πå„πºâŸªÉ«¬∫“ß°≈ÿࡧ◊պ⟪ɫ¬øÕ°‡≈◊Õ¥ ‰¡à·π–π”„Àâ„™â„π°≈ÿà¡Õ◊Ëπ33 4. Vitamin E ¿“«–¢“¥«‘µ“¡‘πÕ’∑”„Àâ osmotic fragility ¢Õ߇¡Á¥‡≈◊Õ¥·¥ß‡æ‘Ë¡¢÷Èπ °“√„Àâ«‘µ“¡‘πÕ’Õ“®¡’ º≈ antioxidant ∑”„Àâ red blood cell survival ¬“«¢÷Èπ ¡’°“√π” vitamin E-bonded dialyzer ¡“„™â æ∫«à“  “¡“√∂≈¥¢π“¥¢Õß ESA ‰¥âÀ≈—ß„™â‰ª 1 ª5ï 0  à«π°“√°‘π«‘µ“¡‘πÕ’ ‰¡à¡’°“√»÷°…“„πºâŸªÉ«¬∑’ˉ¥â√—∫ ESA 49 ·µà¡’¢âÕ¡Ÿ≈„πºâŸªÉ«¬øÕ°‡≈◊Õ¥∑’Ë °‘π«‘µ“¡‘πÕ’ 6 ™¡. °àÕπøÕ°‡≈◊Õ¥ æ∫«à“ “¡“√∂≈¥ lipid peroxidation ‰¥â„πºâŸªÉ«¬∑’ˉ¥â√—∫ IV iron „π EBPG ·π–π”«à“°“√°‘π«‘µ“¡‘πÕ’ 1200 mg §√—È߇¥’¬«°àÕπøÕ°‡≈◊Õ¥ 6 ™¡. „πºŸâªÉ«¬∑’ˉ¥â√—∫ IV iron Õ“® ™à«¬ªÑÕß°—π oxidative stress-related disease „π√–¬–¬“«‰¥â33 5. Statins ¡º’ ≈ anti-inflammatory, antioxidation ·≈– cytoprotection ¡°’ “√»°÷ …“∑æ’Ë ∫«“à statins  “¡“√∂ ≈¥¢π“¥¢Õß ESA ‰¥â√âÕ¬≈– 25 ·≈–‡æ‘Ë¡ Hb ‰¥â√âÕ¬≈– 18 ·µà¢âÕ¡≈Ÿ ¬—ß¡’πâÕ¬ 49,50 6. Oxpentifylline ¡’º≈ anti-inflammation Õ“®¡’ª√–‚¬™πå„π°“√√—°…“¿“«–´’¥ ¡’°“√»÷°…“‚¥¬ Navarro ·≈– §≥– „πºâŸªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß ∑’Ë¡’§à“ creatinine clearance πâÕ¬°«à“ 30 ml/min ‚¥¬„Àâ oxpentifylline 400 mg µàÕ«—𠇪ìπ‡«≈“π“π 6 ‡¥◊Õπ æ∫«à“ Hb ‡æ‘Ë¡¢÷Èπ®“° 9.9±0.5 g/dL ‡ªìπ 10.6±0.6 g/dL, p< 0.01 ·≈– TNF-α ≈¥≈ßÕ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘µ‘ Õ’°°“√»÷°…“„πºâŸªÉ«¬øÕ°‡≈◊Õ¥∑’ˉ¡àµÕ∫ πÕßµàÕ ESA æ∫«à“∑’Ë 4 ‡¥◊Õπ ºâŸªÉ«¬∑’ˉ¥â√—∫ oxpentifylline ¡’ Hb ‡æ‘Ë¡¢÷ÈπÕ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘µ‘ ·µà‡ªìπ‡æ’¬ß°“√»÷°…“¢π“¥ ‡≈°Á 50 Õ¬“à ߉√°µÁ “¡§«√¡°’ “√»°÷ …“‡æ¡Ë‘ ‡µ¡‘ ∂ß÷ ª√–‚¬™π°å Õà π∑®Ë’ –π”¡“„™√â °— …“¿“«–´¥’ „πºªŸâ «É ¬‰µ«“¬ ‡√◊ÈÕ√—ß 181

Practical Dialysis in the Year 2009 7. Resistant to ESA therapy „πºªâŸ «É ¬‰µ«“¬‡√Õ◊È √ß— ∑‰’Ë ¥√â ∫— °“√√°— …“¥«â ¬ESA æ∫«“à ¡®’ ”π«πÀπß÷Ë ∑‰’Ë ¡ à “¡“√∂ achieve target Hb ‰¥â·¡â„Àâ¢π“¥‡µÁ¡∑’Ë·≈â« ®“°°“√»÷°…“„πºâŸªÉ«¬∑’ˇ√‘Ë¡‰¥â√—∫°“√√—°…“¥â«¬ dialysis ·≈–¡’™’«‘µ√Õ¥∑’Ë 6 ‡¥◊Õπ æ∫«à“ √âÕ¬≈– 42 ¡’§à“‡©≈’ˬ Hct πâÕ¬°«à“√âÕ¬≈– 30 ·≈–√âÕ¬≈– 86 ¡’§à“‡©≈’ˬ Hct πâÕ¬°«à“√âÕ¬ ≈– 33 Õ’°°“√»÷°…“„π™à«ßªï 1998-2000 æ∫«à“√âÕ¬≈– 13 ¡’§à“‡©≈’ˬ Hb πâÕ¬°«à“ 10 g/dL ·≈–√âÕ¬≈– 25 ¢Õߺ⟪ɫ¬øÕ°‡≈◊Õ¥ ¡’ Hb πâÕ¬°«à“ 11 g/dL ·≈–√âÕ¬≈– 10 ¡’§à“‡©≈’ˬ Hb πâÕ¬°«à“ 10 g/dL „π°“√  ”√«® ªï 200252 Õ’°°“√»÷°…“ºâŸªÉ«¬øÕ°‡≈◊Õ¥ 130,544 √“¬ ∑’ˇ√‘Ë¡øÕ°‡≈◊Õ¥„πªï 1996-2000 æ∫«à“√âÕ¬≈– 7 ¡’¿“«– intractable anemia ·≈–æ∫«à“ºŸâªÉ«¬ aplastic anemia, chronic blood loss, AIDS, ¡’°“√µ‘¥‡™◊ÈÕ ¡’ ‚Õ°“ ∑®Ë’ –‡°¥‘ intractable anemia ·≈–„πºªâŸ «É ¬°≈¡àÿ intractable anemia ¡Õ’ µ— √“°“√„™â IV iron µ”Ë πÕ°®“° π’È ‚√§√à«¡, multiple catheter insertion, °“√‡¢â“√—∫°“√√—°…“„π‚√ß欓∫“≈¥â«¬ “‡Àµÿ°“√µ‘¥‡™◊ÈÕ ‡æ‘Ë¡ §«“¡‡ ’ˬß∑’Ë®–‡°‘¥¿“«– intractable anemia53 ®“° DOQI „Àâ𑬓¡ resistant to ESA §◊Õ ‰¡à “¡“√∂∑’Ë®–‰¥â target Hb ‡¡◊ËÕ‰¥â epoetin ¡“° °«“à 300 IU/kg/week (20,000 IU/week) À√Õ◊ darbepoetin 100 µg/week À√Õ◊ µÕâ ß„™¬â “¢π“¥π„’È π°“√ maintain Hb54 EBPG ·π–π”„ÀâÀ“ “‡Àµÿ¢Õß hyporesponsiveness to ESA ∂â“ Hb µË”°«à“ 11 g/dL ‡¡◊ËÕ„™â epoetin ¡“°°«à“ 500 IU/kg/week55 ¢π“¥¢Õß epoetin ∑’Ë„™â„π𑬓¡ hyporesponsiveness À√◊Õ resistant µàÕ ESA „™â ”À√—∫∑—ÈߺŸâ ª«É ¬øÕ°‡≈Õ◊ ¥·≈–≈“â ߉µ∑“ß™Õà ß∑Õâ ß ·µ‚à ¥¬∑«—Ë ‰ªºªŸâ «É ¬∑≈’Ë “â ߉µ∑“ß™Õà ß∑Õâ ß„™âESA ¢π“¥µË”°«“à ºªâŸ «É ¬ ∑’ËøÕ°‡≈◊Õ¥ ¡’§«“¡‡ÀÁπ«à“𑬓¡„πºŸâªÉ«¬≈â“߉µ∑“ß™àÕß∑âÕßÕ“®µâÕß°”Àπ¥¢π“¥¢Õß ESA µË”°«à“ ·µà ¬—߉¡à¡’¢âÕ¡≈Ÿ „π¢≥–π’È®÷ß„™â𑬓¡‡¥’¬«°—π ”À√—∫ºŸâªÉ«¬∑—Èß 2 °≈ÿà¡  “‡Àµÿ¢Õß hyporesponsiveness to ESA ∑’Ëæ∫∫àÕ¬ §◊Õ noncompliance, absolute or functional iron deficiency, inflammation  “‡ÀµÿÕ◊Ëπ ‰¥â·°à inadequate dialysis, hyperparathyroidism, nutrient deficiency (vitamin B12, folate), ACE-I, ARB, Aluminium overload, Ab-mediated pure red cell aplasia, bone marrow disorder, myelosuppressive agent, hemoglobinopathies, hemolysis, hypersplenism56 ®“° NECOSAD-2 (Netherlands corporative study on the adequacy of dialysis-2) »÷°…“ºŸâªÉ«¬ 1,677 √“¬ æ∫«à“ 57 √“¬¡’ inadequate response to epo §‘¥‡ªìπ incidence 16.7/1000 pt. year  “‡Àµ¢ÿ Õß resistance to ESA 1. iron deficiency „π°“√ √â“߇¡Á¥‡≈◊Õ¥·¥ß µâÕß¡’∑—Èß epo ·≈–‡À≈Á° dietary iron À≈—ß®“°∂Ÿ°¥Ÿ¥´÷¡ ®–∂°Ÿ æ“ ‰ª¬—ß carrier protein transferrin ´÷Ëß√âÕ¬≈– 80 ®–∂Ÿ°æ“‰ª∑’ˉ¢°√–¥°Ÿ ‡æ◊ËÕ„™â √â“߇¡Á¥‡≈◊Õ¥·¥ß√âÕ¬≈– 70 ¢Õß body iron store Õ¬Ÿà„π‡¡Á¥‡≈◊Õ¥·¥ß‚¥¬√«¡°—∫ Hb13 182

Current Management of Anemia in Dialysis Patients °“√¢“¥‡À≈Á° ¡’∑—Èß absolute ·≈– functional iron deficiency ´÷Ëß functional deficiency ¡’ iron store ‡æ’¬ßæÕ ·µàª√‘¡“≥‰¡à‡À¡“– ¡∑’Ë®– √â“߇¡Á¥‡≈◊Õ¥·¥ß ¥®Ÿ “° serum ferritin ¡“°°«à“ 500 ng/ml ·≈– transferrin saturation πâÕ¬°«à“√âÕ¬≈– 20 ®“° ESAM European survey on anemia management 2003 æ∫«à“√âÕ¬≈– 34 ¢ÕߺŸâªÉ«¬∑’ˉ¥â√—∫ ESA ‰¡à “¡“√∂‰¥â target Hb ‚¥¬√âÕ¬≈– 51.6 ¡’ inadequate iron store57 ®“°°“√»÷°…“ Prevalence of Anemia in Early Renal Insufficiency Study (PEARI) æ∫«à“ºâŸªÉ«¬ ‰µ«“¬‡√◊ÈÕ√—ß∑’Ë¡’ ferritin πâÕ¬°«à“ 100 ng/ml √âÕ¬≈– 49.6 ·≈–∑’Ë¡’ transferrin saturation (TSAT) πâÕ¬ °«à“√âÕ¬≈– 20 ·≈–‡¡◊ËÕ ferritin ¡’§à“πâÕ¬°«à“√âÕ¬≈– 42 · ¥ß«à“ºâŸªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß¡’ iron store µË”3 ·≈–®“° US survey æ∫«à“πâÕ¬°«à“√âÕ¬≈– 55 ¢ÕߺŸâªÉ«¬øÕ°‡≈◊Õ¥ ·≈– πâÕ¬°«à“√âÕ¬≈– 10 ¢Õߺ⟪ɫ¬≈â“߉µ∑“ß™àÕß∑âÕß∑’ˉ¥â√—∫ IV iron ·≈–„πºâŸªÉ«¬øÕ°‡≈◊Õ¥¡’‚Õ°“ ¢“¥‡À≈Á°¡“°°«à“ºâŸªÉ«¬ ≈â“߉µ∑“ß™àÕß∑âÕ߇π◊ËÕß®“°¡’°“√ Ÿ≠‡ ’¬‡≈◊Õ¥¡“°°«à“ ‚¥¬‡©≈’ˬ Ÿ≠‡ ’¬ª√–¡“≥ 2.5 ≈‘µ√µàÕªï §‘¥ ‡ªìπ‡À≈Á° 1000 mg50 Iron deficiency ‡ªπì  “‡Àµ∑ÿ æ’Ë ∫∫Õà ¬∑ ’Ë ¥ÿ ¢Õß hyporesponsiveness to ESA „πºªâŸ «É ¬ dialysis10,50 ¥—ßπ—Èπ DOQI ·π–π”°“√ª√–‡¡‘π iron status °àÕπ‡√‘Ë¡√—°…“¿“«–´’¥ ·≈–∑ÿ°‡¥◊Õπ‡¡◊ËÕ‡√‘Ë¡„Àâ ESA ·≈–  ¡Ë”‡ ¡ÕÕ¬à“ßπâÕ¬∑ÿ° 3 ‡¥◊Õπ‡¡◊ËÕ„Àâ ESA ·≈â« ¿“«–∑Ë’§«√µ√«® iron status ∫àÕ¬¢÷Èπ58 1. ‡√‘Ë¡„Àâ ESA 2. ‰¡à “¡“√∂‰¥â target Hb ™à«ß∑’ˉ¥â√—∫ ESA ·≈â« 3. recent bleeding 4. À≈—ßºà“µ—¥ 5. À≈—ß®“°‡¢â“√—∫°“√√—°…“„π‚√ß欓∫“≈ 6. µ‘¥µ“¡À≈—ß®“°‰¥â IV iron 7. ª√–‡¡‘π ESA hyporesponsiveness  “‡Àµ¢ÿ Õß iron deficiency „πºâªŸ É«¬‰µ«“¬‡√È◊Õ√—ß48 1. °‘πÕ“À“√∑’Ë¡’‡À≈Á°‰¡à‡æ’¬ßæÕ 2. ¡’°“√ ≠Ÿ ‡ ’¬‡≈◊Õ¥‰ª„π extracorporeal circuit 3. ¡’°“√ ≠Ÿ ‡ ’¬‡≈◊Õ¥‰ª„π∑“߇¥‘πÕ“À“√ 4. ‡®“–‡≈◊Õ¥µ√«®∫àÕ¬ 5. °“√¥¥Ÿ ´÷¡‡À≈Á°∑“ß≈”‰ â‰¡à¥’ 6. ¡’°“√¬—∫¬—Èß°“√ª≈àÕ¬‡À≈Á°®“° macrophage 7. ¡’§«“¡µâÕß°“√„™â‡À≈Á°¡“°¢÷Èπ„π™à«ß∑’ˉ¥â√—∫ ESA °“√ª√–‡¡‘π iron status ‡ªìπ°“√ª√–‡¡‘π√–¥—∫‡À≈Á°„π store ·≈–§«“¡‡æ’¬ßæÕ¢Õ߇À≈Á°∑’Ë ®–𔉪„™â„π°“√ √â“√߇¡Á¥‡≈◊Õ¥·¥ß ∑”‰¥â‚¥¬°“√µ√«® serum ferritin, transferrin saturation (TSAT), 183

Practical Dialysis in the Year 2009 percent of hypochromic red blood cell, reticulocyte Hb content (CHr) DOQI ·π–π”„Àâ√—°…“√–¥—∫ iron status ‚¥¬„Àâ serum ferritin ¡“°°«à“ 200 ng/ml, TSAT ¡“°°«à“√âÕ¬≈– 20 À√◊Õ CHr ¡“°°«à“ 29 pg/cell „πºŸâªÉ«¬øÕ°‡≈◊Õ¥  ”À√—∫ºŸâªÉ«¬≈â“߉µ∑“ß™àÕß∑âÕß „Àâ serum ferritin ¡“°°«à“ 100 ng/ml ·≈– TSAT ¡“°°«à“√âÕ¬≈– 20, upper limit ¢Õß serum ferritin  ”À√—∫„Àâ IV iron §◊Õ 500 ng/ml58 serum ferritin „™âª√–‡¡‘π iron store ‚¥¬„πºâŸªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß „™â cut-off point 100 ng/ml ‡π◊ËÕß®“°„π¿“«–∑’Ë¡’ inflammation, ¡–‡√Áß, ‚√§µ—∫ §à“π’È®–‡æ‘Ë¡¢÷Èπ 3 ‡∑à“¢Õß§à“ª°µ‘48 ∂â“√–¥—∫πâÕ¬°«à“ 20 ng/ml · ¥ß«à“¢“¥‡À≈Á° §à“ ferritin ∑’˵√«®À≈—ß°“√„Àâ IV iron Õ“®‰¡à∫àß∂÷ß iron status ∂â“„Àâ IV iron ¢π“¥ Ÿß À√◊Õ‡®“–À≈—ß„Àâ IV iron ‰¡àπ“π ¥—ßπ—Èπ EBPG ·π–π”„Àâ√ÕÕ¬à“ßπâÕ¬ 1  —ª¥“ÀåÀ≈—ß„Àâ IV iron ¡“°°«à“ 100 mg /dose °“√ª√–‡¡‘π availability of iron store: percent of hypochromic red blood cell (HRC), Hb content of reticulocyte, TSAT11,59 HRC §◊Õ ‡´≈≈å∑’Ë¡’ Hb content πâÕ¬°«à“ 28 g/dL §à“ª°µ‘πâÕ¬°«à“√âÕ¬≈– 2.5 ∂â“√âÕ¬≈– 2.5- 10 · ¥ß«à“ indeterminate measurement, ¡“°°«à“√âÕ¬≈– 10 · ¥ß«à“ definite functional iron deficiency ·µàªí≠À“§◊Õ‡§√◊ËÕß¡◊Õ∑’Ë„™â«—¥ ‰¡à¡’·æ√àÀ≈“¬ TSAT §”π«≥®“° serum iron / total iron binding capacity ‡ªìπ§à“∑’Ë∫àß∫Õ° iron availability ¿“«–∑’Ë¡’º≈µàÕ§à“ TSAT ‚¥¬‰¡à‰¥â‡°‘¥®“°°“√‡ª≈’ˬπ·ª≈ߢÕß iron status 1. acute and chronic inflammation ∑”„Àâ§à“ TSAT ≈¥≈ß 2. bone marrow dysfunction ®“° alcohol, cancer, megaloblastic process ∑”„Àâ§à“ TSAT  Ÿß ¢÷Èπ CHr «¥— volume ·≈– Hb concentration „π reticulocyte ∫Õ°∂ß÷ level of effective erythropoiesis ¡’ day to day variation √âÕ¬≈– 3.4 ·≈–§à“ª°µ‘πâÕ¬°«à“ 26 pg ∂â“«—¥‚¥¬‡§√◊ËÕß H*3 automated blood count analyzer À√◊ÕπâÕ¬°«à“ 29 pg ∂â“„™â‡§√Ë◊Õß ADVIA §à“π’ș૬„π°“√«‘π‘®©—¬¿“«– functional iron deficiency ·≈–¡’ inverse relationship °—∫¢π“¥¢Õß ESA Lab parameter Õ◊ËπÊ ‰¥â·°à Zinc protoporphyrin (ZPP) „π¿“«–∑’Ë¢“¥‡À≈Á° Zinc ®–·∑π∑’Ë ‡À≈Á°„π protoporphyrin IX ‰¥â‡ªìπ ZPP  “¡“√∂∫Õ° iron store, availability ‰¥â·µà‰¡à¥’‡∑à“ HRC ∂â“§à“‡æ‘Ë¡ ¢÷Èπ · ¥ß«à“¢“¥‡À≈Á°∑’Ë√–¬–°“√ √â“߇¡Á¥‡≈◊Õ¥·¥ß ·µà‰¡à‡®“–®ß ”À√—∫¢“¥‡À≈Á°2 Soluble transferrin receptor (sTfR) ∫Õ°∂÷ß®”π«π erythroblast „π‰¢°√–¥Ÿ° ·≈– total erythroid activity √–¥—∫®–‡æ‘Ë¡¢÷Èπ„π§π∑’ˉ¥â ESA ·≈–¡’ iron deficiency ¬—߉¡à¡’¢âÕ¡Ÿ≈°“√„™â„πºâŸªÉ«¬‰µ «“¬‡√◊ÈÕ√—ß ‡¡◊ËÕ‡ª√’¬∫‡∑’¬∫·µà≈– parameter æ∫«à“ CHr ¥’°«à“ ferritin ·≈– TSAT ‡π◊ËÕß®“° CHr ∫Õ°∂÷ß integrated effect of iron store, inflammation ·≈– erythropoietic stimulation on iron availability „πºŸâªÉ«¬ øÕ°‡≈◊Õ¥ ∂Ⓡª√’¬∫‡∑’¬∫√–À«à“ß CHr °—∫ HRC ∫“ß°“√»÷°…“æ∫«à“ CHr ¥’°«à“„π°“√ detect iron deficiency  à«π HRC ¥’∑’Ë ÿ¥„π°“√ª√–‡¡‘π¿“«– functional iron deficiency  “¡“√∂·¬°ºŸâªÉ«¬øÕ°‡≈◊Õ¥ 184

Current Management of Anemia in Dialysis Patients ∑’Ë®–µÕ∫ πÕßµàÕ IV iron ‰¥â ‚¥¬¡’ efficiency √âÕ¬≈– 89.6 ∑’Ë cut-off √âÕ¬≈– 6, ‡∑’¬∫°—∫ CHr ¡’ efficiency √âÕ¬≈– 78.4 ∑’Ë cut-off 29 pg, TSAT ¡’ efficiency √âÕ¬≈– 70.4 ∑’Ë cut-off √âÕ¬≈– 19 ·≈– ferritin ¡’ efficiency √âÕ¬≈– 6 ∑’Ë cut-off 50 ng/ml59 °“√¡’ iron store ∑’ˇ撬ßæÕ ®–™à«¬„ÀâµÕ∫ πÕßµàÕ ESA ¥’ De vital ·≈–§≥– æ∫«à“ºâŸªÉ«¬ øÕ°‡≈◊Õ¥∑’ˉ¥â ESA ·≈– IV iron ºâŸªÉ«¬∑’Ë¡’ serum ferritin 400 ng/ml ®–¡’ Hb  ßŸ °«à“ ·≈–„™â¢π“¥¢Õß ESA µË”°«à“ºâŸªÉ«¬∑’Ë¡’ ferritin 200 ng/ml °“√»÷°…“‚¥¬ Besarab ·≈–§≥– æ∫«à“ºŸâªÉ«¬∑’Ë TSAT √âÕ¬≈– 30-50 ®–„™â¢π“¥¢Õß ESA µË”°«à“ TSAT √âÕ¬≈– 20-30 ∂÷ß 40 ·≈–®“° CARI guideline ·π–π”„Àâ√–¥—∫ ferritin 200-500 ng/ml, TSAT √âÕ¬≈– 30-40 50 °“√„Àâ Iron ¡’ 2 «‘∏’ §◊Õ 1. ∑“ß°“√°‘𠇪ìπ«‘∏’∑’Ëßà“¬  –¥«° ·≈–√“§“∂Ÿ°12 ¢π“¥¢Õß ferrous sulfate 200 mg «—π ≈– 3 §√—Èß ªí≠À“§◊Õ„πºŸâªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß¡—°¡’°“√¥¥Ÿ ´÷¡‡À≈Á°∑’Ë∑“߇¥‘πÕ“À“√‰¥â‰¡à¥’ Õ“®∂Ÿ° interfere °“√¥Ÿ¥´÷¡‚¥¬¬“∫“ß™π‘¥‡™àπ phosphate binder, H2 blocker À√◊Õ¡’°“√ Ÿ≠‡ ’¬‡≈◊Õ¥„π∑“߇¥‘πÕ“À“√ ∑”„Àâª√‘¡“≥‡À≈Á°∑’ˉ¥â®“°°“√°‘π·≈–¥Ÿ¥´÷¡‰¡à‡æ’¬ßæÕ ¢âÕ¡Ÿ≈®“° Australian survey of anemia management æ∫«“à „πºªŸâ «É ¬≈“â ߉µ∑“ß™Õà ß∑Õâ ß 1295 √“¬ ∑‰Ë’ ¥√â ∫— ‡À≈°Á ‚¥¬°“√°π‘ ¡’ Hb µ”Ë , lower TSAT, serum ferritin ·≈–µâÕß„™â ESA ¢π“¥ Ÿß57 ·µà‡π◊ËÕß®“°§«“¡ –¥«° „πºâŸªÉ«¬≈â“߉µ∑“ß™àÕß∑âÕß ¬—ß  “¡“√∂„Àâ°‘π‡À≈Á°‰¥5â 8 º≈¢â“߇§’¬ß®“°°“√°‘π‡À≈Á°¡’æÕ ¡§«√ „πºâŸªÉ«¬∫“ß√“¬Õ“®‰¡à “¡“√∂∑πº≈¢â“߇§’¬ß∑’Ë ‡°‘¥¢÷Èπ‰¥â º≈¢â“߇§’¬ß‰¥â·°à ∑âÕߺŸ° ª«¥∑âÕß √⟠÷°‰¡à ∫“¬∑âÕß ∫“ß√“¬ß“πæ∫∂÷ß√âÕ¬≈– 50 ¢ÕߺŸâªÉ«¬ ∑’Ë¡’º≈¢â“߇§’¬ß Õ“®¡’º≈µàÕ compliance ·≈–¿“«–‚¿™π“°“√‰¥5â 7 Õ“®·°â‰¢‚¥¬°‘π„π¢≥–∑âÕß«à“ß 2 ™¡.°àÕπÀ√◊Õ 1 ™¡.À≈—ßÕ“À“√ ‡æ◊ËÕ‡æ‘Ë¡°“√¥Ÿ¥´÷¡ À√◊Õ°‘π°àÕππÕπ À√◊Õ≈¥¢π“¥¢Õ߬“‡æ◊ËÕ≈¥º≈¢â“ß ‡§’¬ß60 2. IV iron ™π‘¥¢Õß IV iron ∑’Ë¡’„™â §◊Õ dextran, sodium ferric gluconate, iron sucrose °“√„Àâ IV iron ™à«¬≈¥ªí≠À“‡√◊ËÕß°“√¥¥Ÿ ´÷¡À√◊Õº≈¢â“߇§’¬ß®“°°“√°‘π‡À≈Á° ‡ªìπ optimum route ¢Õß°“√„Àâ ‡À≈Á°„πºâŸªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß ®“°°“√»÷°…“¢Õß Ahsan ·≈–§≥– æ∫«à“„πºŸâªÉ«¬≈â“߉µ∑“ß™àÕß∑âÕß∑’Ë°‘π ‡À≈Á°π“π 3 ‡¥◊Õπ·≈⫬—߉¡à‰¥â target Hb æ∫«à“‡¡◊ËÕ„Àâ IV iron dextran 1 g  “¡“√∂‡æ‘Ë¡§à“ Hct ·≈– TSAT ‰¥âÕ¬à“ß¡’π—¬ ”§—≠∑’Ë 6 ‡¥◊Õπ °“√»÷°…“‚¥¬ Singh H ·≈–§≥–„πºâŸªÉ«¬≈â“߉µ∑“ß™àÕß∑âÕß 126 √“¬ ∑’Ë¡’ªí≠À“´’¥·≈–¡’ TSAT πâÕ¬°«à“√âÕ¬≈– 25 ·≈– ferritin πâÕ¬°«à“À√◊Õ‡∑à“°—∫ 500 ng/ml ‡¡◊ËÕ„Àâ IV iron sucrose 300 mg „π 1.5 ™¡. „π«—π∑’Ë 1, 15 Õ’°°≈ÿà¡„Àâ IV iron sucrose 400 mg „π 2.5 ™¡. „π«—π∑’Ë 29 ‡∑’¬∫°—∫°≈ÿà¡∑’ˉ¡à‰¥â„Àâ ‡À≈Á° æ∫«à“°≈ÿà¡∑’ˉ¥â IV iron ¡’ Hb ‡æ‘Ë¡¢÷Èπ·≈–≈¥¢π“¥¢Õß ESA ‡¡◊ËÕ‡∑’¬∫°—∫°≈ÿà¡∑’ˉ¡à„Àâ ‚¥¬‰¡àæ∫º≈ ¢â“߇§’¬ß·≈–°“√µ‘¥‡™◊ÈÕ47 ¢âÕ¡≈Ÿ ®“° Australian survey of anemia management ¬◊π¬—π«à“„πºâŸªÉ«¬≈â“߉µ∑“ß™àÕß∑âÕß ∑’Ë¢“¥‡À≈Á° ‡¡◊ËÕ‰¥â√—∫ IV iron ¡’ hematological response ¥’¢÷Èπ 57 „πºŸâªÉ«¬∑’Ë¡’ TSAT µË”°«à“√âÕ¬≈– 20 ·≈– ferritin ¡“°°«à“ 500 ng/ml ´÷Ëß¡—°‡°‘¥®“°¿“«– 185

Practical Dialysis in the Year 2009 Õ—°‡ ∫ °“√„Àâ IV iron ¡’¢âÕ§«√√–«—ß «à“Õ“®‰¡à™à«¬ ·≈–Õ“®¡’Õ—πµ√“¬®“° proinflammatory effect ¢Õß IV iron ®“°°“√»°÷ …“ bone marrow iron, liver iron „πºªŸâ «É ¬‰µ«“¬‡√ÕÈ◊ √ß— æ∫«“à ‰¡¡à º’ ªâŸ «É ¬§π„¥∑¡Ë’ ’ serum ferritin ¡“°°«à“ 500 ng/ml ·≈â«¡’ absent bone marrow iron store ·≈–¬—ßæ∫«à“„πºâŸªÉ«¬øÕ°‡≈◊Õ¥∑’Ë¡’ serum ferritin ¡“°°«à“ 500 ng/ml ¡’ hepatic-non-heme iron concentration ¡“°°«à“ upper limit ¢Õß§à“ ª°µ‘ ¥—ßπ—Èπ°“√„Àâ IV iron „πºâŸªÉ«¬∑’Ë ferritin ¡“°°«à“ 500 ng/ml §«√æ‘®“√≥“ clinical status ¢ÕߺŸâªÉ«¬ ‡™àπ ∂â“ ferritin ¡“°°«à“ 500 ng/ml ‚¥¬ TSAT µË”°«à“√âÕ¬≈– 20 Õ“®¡’ functional iron deficiency Õ“® ∑¥≈Õß„Àâ 1 course ¢Õß IV iron58 °“√»÷°…“∑’Ë„Àâ IV iron „πºâŸªÉ«¬∑’Ë¡’√–¥—∫ ferritin  Ÿß ®“° DRIVE study »÷°…“ºŸâªÉ«¬ dialysis 134 √“¬∑’Ë¡’ Hb πâÕ¬°«à“ 11 g/dL ·≈–¡’ ferritin 500-1,200 ng/ml, TSAT πâÕ¬°«à“√âÕ¬≈– 25 ·≈–‰¥â epoetin ¡“°°«à“À√◊Õ‡∑à“°—∫ 225 IU/kg/week ‡ª√’¬∫‡∑’¬∫°“√„Àâ ferric gluconate 125 mg IV ∑ÿ° hemodialysis session ‡∑’¬∫°—∫°≈ÿࡧ«∫§ÿ¡ æ∫«à“∑’Ë 6  —ª¥“Àå §à“‡©≈’ˬ Hb „π°≈ÿà¡∑’ˉ¥â IV iron ‡∑à“°—∫ 16±1.3 g/dL ‡∑’¬∫°—∫ 11±1.4 g/dL „π°≈ÿࡧ«∫§ÿ¡, p=0.028 ‚¥¬‰¡à‰¥âæ∫º≈¢â“߇§’¬ß‡æ‘Ë¡¢÷Èπ50 ·≈–„π DRIVE II ‡¡◊ËÕ¢¬“¬‡«≈“µ‘¥µ“¡ºâŸªÉ«¬µàÕ‰ªÕ’° 6  —ª¥“Àå æ∫«à“„π°≈ÿà¡∑’ˉ¥â IV iron  “¡“√∂≈¥¢π“¥ ¢Õß epoetin ‰¥â√âÕ¬≈– 21 ‚¥¬∑’Ë “¡“√∂ maintain Hb µ“¡∑’˵âÕß°“√ °≈ÿà¡∑’ˉ¥â IV iron √âÕ¬≈– 83.9  “¡“√∂ maintain Hb ¡“°°«à“ 11 g/dL ‰¥â „π¢≥–∑’Ë°≈ÿࡧ«∫§ÿ¡¡’‡æ’¬ß√âÕ¬≈– 67.9 ∑’Ë maintain ‰¥â °≈ÿà¡ ∑‰Ë’ ¥â IV iron ¡º’ ≈¢“â ߇§¬’ ßπÕâ ¬°«“à ·≈–Õµ— √“°“√‡¢“â √∫— °“√√°— …“„π‚√ß欓∫“≈®“°°“√µ¥‘ ‡™ÕÈ◊ µ”Ë °«“à 61 «∏‘ °’ “√„Àâ IV iron ¡’ 2 «‘∏’ §◊Õ 1. periodic iron repletion „Àâ IV iron ‡ªìπ§√—ÈßÊ ‡¡◊ËÕ iron status µË”≈ß 2. continuous maintenance treatment „Àâ small dose Õ¬à“ß ¡Ë”‡ ¡Õ „Àâ iron status §ß∑’Ë„π √–¥—∫‡ªÑ“À¡“¬ ‰¡¡à °’ “√»°÷ …“‡ª√¬’ ∫‡∑¬’ ∫ª√– ∑‘ ∏¿‘ “æ¢Õß°“√„À∑â ß—È 2 «∏‘ ’ ¢π“¥‡©≈¬’Ë ¢Õß IV iron ∑ ’Ë “¡“√∂ maintain „Àâ serum ferritin §ß∑’ˉ¥â §◊Õ 22-65 mg µàÕ —ª¥“Àå „πºâŸªÉ«¬øÕ°‡≈◊Õ¥ Õ“®„Àâ 20-60 mg/session ∫“ß·Ààß°Á„Àâ 100-200 mg/week À√◊Õ µàÕ‡¥◊Õπ „πºâŸªÉ«¬≈â“߉µ∑“ß™àÕß∑âÕß Õ“®„Àâ∑ÿ° —ª¥“ÀåÀ√◊Õ∑ÿ°‡¥◊Õπ „π™à«ß maintenance Õ“®„Àâ∑ÿ° 3 ‡¥◊Õπ ®“° EBPG ·π–π”„Àâ optimum iron dose 25-150 mg/week „π 6 ‡¥◊Õπ·√°¢Õß°“√„Àâ ESA33 Maximal FDA-approved dose for single administration47 Dose 100 mg „π 2 π“∑’ Dose 200 mg „π 2-5 π“∑’ Dose 300 mg „π 1.5 ™¡. Dose 400 mg „π 2.5 ™¡. º≈¢“â ߇§¬’ ߢÕß IV iron °“√„Àâ IV iron Õ“®∑”„À⇰‘¥ acute free-iron reaction ¡’ hypotension, dyspnea, arhralgia, myalgia, nausea, vomiting, abdominal pain ´÷Ë߇ªìπ rate ·≈– dose dependent ∂â“„Àâ¢π“¥πâÕ¬°«à“ 300 186

Current Management of Anemia in Dialysis Patients mg50 ®–‰¡à§àÕ¬æ∫º≈¢â“߇§’¬ß anaphylactoid reaction ¡’√“¬ß“πæ∫„πºâŸªÉ«¬∑’ˉ¥â√—∫ iron dextran ‡∑à“π—Èπ ª√–¡“≥√âÕ¬≈– 0.7 ∂⓺ŸâªÉ«¬¡’º≈¢â“߇§’¬ßπ’È®“°°“√‰¥â√—∫ iron dextran  “¡“√∂„™â iron sucrose À√◊Õ ferric gluconate ·∑π‰¥â delayed reaction: arthralgia, myalgia, fever, malaise æ∫‰¥â„πºŸâªÉ«¬∑’ˉ¥â√—∫ iron dextran iron  “¡“√∂ – ¡„πµ—∫ À—«„®‰¥â ·µà¬—߉¡à¡’¢âÕ¡≈Ÿ ™—¥‡®π∂÷ߺ≈‡ ’¬„π√–¬–¬“«13 taste disturbance æ∫√âÕ¬≈– 8.4 infection ®“°¢âÕ¡≈Ÿ ¢Õß EPIBACDIAL ºŸâªÉ«¬øÕ°‡≈◊Õ¥ 998 √“¬ æ∫«à“¿“«–´’¥ ‡æ‘Ë¡§«“¡ ‡ ’ˬ߄π°“√µ‘¥‡™◊ÈÕ ·µà‰¡à —¡æ—π∏å°—∫°“√„Àâ IV iron50 2. Hyperparathyroidism Parathyroid hormone ¡’º≈¬—∫¬—Èß BFU-E in vitro ·≈–∑”„À⇰‘¥ bone marrow fibrosis ·≈– ‡æ‘Ë¡ red blood cell fragility ¡’º≈¬—∫¬—Èß epo synthesis ·≈– erythroid progenitor ‚¥¬µ√ß Mandelfo ·≈– §≥– »÷°…“„πºâŸªÉ«¬øÕ°‡≈◊Õ¥ 19 √“¬ æ∫«à“À≈—ß®“°∑” parathyroidectomy §à“ Hb ‡æ‘Ë¡¢÷Èπ√âÕ¬≈– 20 ·≈–≈¥¢π“¥¢Õß epoetin ‰¥â√âÕ¬≈– 3450 3. Aluminium intoxication Aluminium ¡’º≈√∫°«π°“√ √â“ß heme ·≈– disruption iron transport ∑”„À≡àµÕ∫ πÕßµàÕ ESA °“√„Àâ deferioxamine chelation ¡’√“¬ß“π«à“™à«¬„π°“√µÕ∫ πÕßµàÕ ESA ‰¥â„π∫“ß√“¬ ·µà¬—ß¡’ ªí≠À“‡√◊ËÕߺ≈¢â“߇§’¬ß ‡™àπ visual toxicity50 4. Blood loss, hemolysis µ”·Àπàß∑’Ë¡’°“√ ≠Ÿ ‡ ’¬‡≈◊Õ¥„πºŸâªÉ«¬‰µ«“¬‡√◊ÈÕ√—ß ‰¥â·°à ∑“߇¥‘πÕ“À“√ ∂â“„πºŸâªÉ«¬À≠‘ß Õ“®®“°°“√¡’ª√–®”‡¥◊Õπ Hemolysis ¡—°æ∫„π°√≥’∑’Ë dialysate ¡’°“√ªπ‡ªóôÕπ chloramine, °“√„™â formaldehyde „π °“√ reuse ‚¥¬∑”„À⇰‘¥ anti E Ab °“√æ—≤π“‡∑§π‘§°“√≈â“߉µ∑”„Àâªí≠À“¥—ß°≈à“«≈¥≈ß¡“° 5. Hemoglobinopathies Thalassemia, Sickle cell anemia  “¡“√∂«‘π‘®©—¬‰¥â¥â«¬°“√¥Ÿ red blood cell morphology ·≈– Hb electrophoresis 6. Vitamin deficiency: vitamin B 12, vitamin B6, folate „πºŸâªÉ«¬ dialysis ·¡â«à“¡’°“√ ≠Ÿ ‡ ’¬ folate ‰ª„π dialysate ·≈–¡’§«“¡µâÕß°“√¡“°¢÷Èπ‡¡◊ËÕ ‡√¡‘Ë „Àâ ESA ·µ¡à °— ‰¡¢à “¥∂“â ¡¿’ “«–‚¿™π“°“√¥’ Schiffl H. ‰¥»â °÷ …“ºªŸâ «É ¬øÕ°‡≈Õ◊ ¥10 √“¬ ∑¡’Ë ’ macrocytic anemia „Àâ IV folic acid 20mg 3 §√—ÈßµàÕ —ª¥“Àå æ∫«à“‡¡◊ËÕ‰¥â folic acid §à“ Hb  Ÿß¢÷Èπ¡“„π‡°≥±åª°µ‘ 187